The paraventricular nucleus of the hypothalamus plays a pivotol role in the regulation of plasma volume. Part of the response to an increase in volume load is an inhibition of renal sympathetic nerve activity. The present experiments were designed to determine which subnuclei of the paraventricular nucleus are involved in this sympatho-inhibitory response. Experiments were performed on anaesthetised rats. Activated neurones were recognised by the expression of the early gene c-fos, identified by immunohistochemical labelling of its protein product Fos. Plasma volume loading with 4 % Ficoll 70, using an infusion-withdrawal procedure (2 ml over 1 min) repeated 15 times over 1 h revealed a total of 775 ± 101 (n = 6) Fos-positive neurones scattered throughout both the magnocellular and parvocellular subnuclei. In comparison, sustained hypertension resulted in 452 ± 56 (n = 3) Fos-positive neurones similarly distributed, whereas a normotensive control group (n = 3) displayed 115 ± 18 Fos-positive neurones. Because of this lack of a specific effect we used a more selective stimulation of right atrial receptors via a balloon placed at the junction of the superior vena cava and the right atrium so it did not impede venous return. Inflation of the balloon inhibited renal sympathetic nerve activity (36 ± 5 %, n = 7) and repetitive inflation over 1 h resulted in c-fos activation of a small number of neurones (54 ± 14) located only in the parvocellular subnuclei. Whether these are inhibitory interneurones acting within the paraventricular nucleus, or spinally projecting neurones which inhibit or excite renal sympathetic activity by an action in the spinal cord remains to be determined. Experimental Physiology (2002) 87.1, 25-32.

In this study we sought to determine whether early myocardial fibrosis is associated with depletion of vasoactive intestinal peptide (VIP) in the heart, thereby suggesting a possible pathogenetic role for depletion of myocardial VIP levels in the development of fibrosis in the heart. Spontaneously hypertensive rats (SHRs) and normotensive control Wistar-Kyoto rats (WKYs) were assigned randomly to low, intermediate or high sodium diets and their blood pressure was recorded twice weekly for 4 weeks. At the end of this period the rats were anaesthetised, blood was sampled for plasma VIP concentration and the hearts were harvested for histology and determination of the concentration of VIP in the heart. The degree of myocardial fibrosis increased with increasing dietary sodium intake in both the WKYs (P < 0.001) and the SHRs (P < 0.01). Myocardial VIP concentration decreased with increasing dietary sodium intake in the WKYs (P < 0.01) and in the SHRs (P < 0.01). There was a negative correlation between myocardial VIP concentration and the degree of myocardial fibrosis in both the WKYs (P < 0.0005) and the SHRs (P < 0.005). Dietary sodium intake induces myocardial fibrosis in a dose-dependent manner. Further, in early myocardial fibrosis resulting from increasing dietary sodium intake in both normotensive and hypertensive rats the concentration of VIP in the heart was negatively correlated with the degree of fibrosis. This suggests a possible role for depletion of VIP in the myocardium in the pathogenesis of myocardial fibrosis. Experimental Physiology (2002) 87.5, 539-546.

It was recently demonstrated that ammonia inhibits sodium absorption in the proximal colon of rats. In order to investigate the effect of luminal ammonia in the distal colon, sodium and chloride transport were measured in Ussing chambers. Under short-circuit conditions, distal colon absorbed sodium and chloride. When luminal ammonia (30 mmol l-1) was present, sodium and chloride absorption was diminished. Inhibition of the two Na+-H+ exchanger isoforms NHE2 and NHE3, which are known to be located in the apical membrane of the distal colon epithelium, failed to influence the effect of ammonia on transepithelial sodium and chloride fluxes. The inhibitory effect of ammonia was eliminated under the following conditions: after block of carbonic anhydrases with acetazolamide, in the presence of an unspecific blocker of Na+-H+ exchangers, and under chloride-free conditions. Ammonia did not alter electrogenic sodium absorption. These results demonstrate that luminal ammonia inhibits sodium and chloride absorption in rat distal colon. We suggest that ammonia inhibits NaCl absorption by interfering with a Na+-H+ exchanger that is not NHE2 or NHE3. Experimental Physiology (2002) 87.3, 311-319.

The cellular mechanisms that underlie the initiation and propagation of the peristaltic contractions, which transport urine from the kidney to the bladder for storage, remain little understood. Extracellular and intracellular microelectrode recordings have identified two populations of smooth muscle cells as well as a population of renal interstitial cells (RICs) that all display spontaneous electrical activity. By analogy with the heart it has been proposed that atypical smooth muscle cells, preferentially located in the very proximal regions of the renal pelvis, generate the essential pacemaker signal. These pacemaker potentials propagate to neighbouring typical smooth muscle cells or RICs to trigger action potential discharge. These action potentials then propagate distally to trigger other bundles of typical smooth muscle cells. The frequency of action potential discharge and contraction decreases as the relative number of RICs and atypical smooth muscle cells compared to typical smooth muscle cells decreases with distance from the renal fornix. It is clear that functional capsaicin-sensitive sensory afferents and the endogenous release of both tachykinins and prostaglandins are essential in the maintenance of normal peristalsis, as well as in monitoring and responding to any chemical or mechanical stimulation. However, the cellular mechanisms underlying the action of these endogenously-released agents remain to be elucidated. Experimental Physiology (2002) 87.2, 129-146.

In this study the effects of changes in extracellular magnesium ([Mg2+]o) and calcium ([Ca2+]o) concentrations on basal and on nerve-mediated and acetylcholine (ACh)-evoked in vitro amylase release and calcium mobilization were investigated in rat parotid gland tissue. In the presence of a normal (2.56 mM) [Ca2+]o, both zero (0 mM) and an elevated (10 mM) [Mg2+]o significantly attenuated basal and ACh-evoked amylase release compared to the response obtained in normal (1.1 mM) [Mg2+]o. During electrical field stimulation (EFS) of parotid tissues, only elevated [Mg2+]o reduced amylase release. In a Ca2+-free medium, both basal and ACh-evoked amylase output were markedly reduced compared to the responses obtained under similar conditions in normal [Ca2+]o. Again, the ACh-induced amylase release in a Ca2+-free solution was larger in normal [Mg2+]o than when the [Mg2+]o was either zero or was elevated to 10 mM. Perturbation of [Mg2+]o had no significant effect on basal intracellular free calcium concentration ([Ca2+]i) in parotid acinar cells loaded with the fluorescent Ca2+ indicator fura-2. Both zero Mg2+ and an elevated [Mg2+]o significantly reduced the ACh-induced rise in the peak and the plateau phase of the Ca2+ transient that was seen in normal [Mg2+]o. In parotid acinar cells loaded with the fluorescent Mg2+ indicator magfura-2, ACh elicited a gradual decrease in intracellular free Mg2+ concentration ([Mg2+]i) to below the basal level. The results indicate that both hypo- and hypermagnesaemia may reduce both basal and ACh-evoked amylase secretion from the salivary gland. As far as the ACh-evoked response is concerned, the effect may be exerted by a decrease in cellular Ca2+ transport. Experimental Physiology (2002) 87.3, 321-326.

The purpose of this study was to determine the influence of testosterone, the male sex hormone, on β-adrenergic agonist-induced amylase secretion from rat parotid glands. Isoprenaline (isoproterenol)-induced amylase secretion was measured in vitro from the parotid glands of control and castrated rats with and without testosterone replacement. The isoprenaline-induced amylase release was reduced in parotid glands from castrated rats compared to controls. The reduction of amylase release by isoprenaline in parotid glands of castrated rats, could be reversed by administration of testosterone. Furthermore, β-adrenergic receptor density and the level of isoprenaline-evoked cAMP in parotid glands from castrated rats was lower compared to intact rats. Using SQ-22536 (an adenylyl cyclase inhibitor), dibutyryl cAMP (a cAMP analogue) and verapamil (a calcium channel blocker), we conclude that the impairment of amylase release from parotid glands after castration was not related to either adenylyl cyclase activity or cAMP accumulation. Amylase release from the parotid glands of castrated rats appears to be mediated by an increase in calcium ion influx.

We established a mouse model of cardiac dysfunction due to myocardial infarction (MI). For this we ligated the left anterior descending coronary artery in male C57BL/6J mice and assessed healing and left ventricular (LV) remodelling at 1, 2 and 4 days and 1, 2 and 4 weeks after MI. Echocardiography was performed at 1 and 2 weeks and 1, 2, 4 and 6 months after MI. We found that neutrophil infiltration of the infarct border was noticeable at 1-2 days. Marked macrophage infiltration occurred at day 4, while lymphocyte infiltration was apparent at 7-14 days. Massive proliferation of fibroblasts and collagen accumulation began by day 7-14, and scar formation was completed by day 21. LV diastolic dimension increased markedly at 2 weeks and remained at the same level thereafter. LV shortening fraction decreased significantly at 2 weeks and then slowly decreased. In non-infarcted areas of the LV, myocyte cross-sectional area and interstitial collagen fraction increased progressively, reaching a maximum at 4 months. This study provides important qualitative and quantitative information about the natural history of cardiac remodelling after MI in mice. Experimental Physiology (2002) 87.5, 547-555.

The sympathetic nervous system is believed to play a major role in regulating cardiovascular function during exercise. However, only a few direct measurements of sympathetic nervous activity during whole body dynamic exercise have been attempted. In the present study, we have established a method to allow routine measurement of renal sympathetic nerve activity (RSNA) and cardiovascular function during treadmill exercise in rats. We trained Wistar rats to run on the treadmill for a week before the surgery. At least 2 days before the experiment, electrodes for recording RSNA, electrocardiogram and electromyogram, and catheters for the measurements of systemic arterial and central venous pressures were implanted under aseptic conditions. Satisfactory signal to noise ratios were obtained in 80 %, 60 % and 40 % of the group at 1-3 days, 4-7 days and 8-10 days after the surgery, respectively. RSNA was successfully recorded without contamination by external noise during treadmill exercise. Treadmill exercise resulted in an abrupt increase in RSNA, by 82 % at 0.5 min, and then reached a stable level of ~40 % during the period of 5-30 min after the onset of treadmill exercise. This experimental model allows us to study the neural mechanisms involved in the regulation of cardiovascular function during dynamic exercise in rats. Experimental Physiology (2002) 87.1, 33-39.

The muscarinic agonist bethanechol was infused intravenously, under α- and β-adrenoceptor blockade, in anaesthetized rats at various dose levels (5-10, 20 and 40-50 µg kg-1 min-1) over 30 min. The amount of saliva secreted from the parotid gland was dose dependent at 95, 202 and 737µl, respectively. The salivary amylase activity was approximately the same at the two lower doses (506 U and 448 U, respectively), while it was higher (1268 U) at the highest dose. In response to the highest dose, but not to the lower doses, the total parotid glandular amylase activity and the numerical density of parotid acinar secretory granules were lowered, by 25 % and 22 %, respectively. Thus, in the rat parotid gland, agonists such as bethanechol, which use Ca2+ as a second messenger, may release proteins not only by non-granular mechanisms but also, and in contrast to the general belief, by granule exocytosis. Experimental Physiology (2002) 87.2, 147-152.

Primary thoracic blast injury causes a triad of bradycardia, hypotension and apnoea mediated in part via a vagal reflex. Blast casualties may also suffer blood loss, and the response to progressive simple haemorrhage is biphasic: an initial tachycardia followed by a vagally mediated reflex bradycardia which can be attenuated by μ opioid agonists. The aims of this study were to determine the effects of thoracic blast injury on the response to subsequent haemorrhage, and the effects of morphine, administered after blast, on the response to blood loss. Male Wistar rats, terminally anaesthetised with alphadolone–alphaxolone (19–21 mg kg−1 h−1 I.V.), were allocated randomly to one of three groups: Group I, sham blast; Group II, thoracic blast; Group III, thoracic blast plus morphine (0.5 mg kg−1 I.V. given 5 min after blast). Blast (Groups II and III) resulted in significant (P<0.05, ANOVA) bradycardia, hypotension and apnoea. Sham blast (Group I) had no effect. Ten minutes later, haemorrhage (40% of the estimated total blood volume (BV)) in Group I produced a biphasic response comprising a tachycardia followed by a peak bradycardia after the loss of 33% BV. Arterial blood pressure did not fall significantly until the loss of 13.3% BV. In Group II the haemorrhage-induced tachycardia was absent and the bradycardia was augmented: peak bradycardia was seen after the loss of 23% BV. Mean arterial blood pressure (MBP) began to fall as soon as haemorrhage commenced and was significant after the loss of 10% BV. Morphine (Group III) prevented the haemorrhage-induced bradycardia and delayed the significant fall in MBP until the loss of 30% BV. It is concluded that the response to thoracic blast injury augments the depressor response to haemorrhage while morphine attenuates this response.

It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible presssor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker α-bungarotoxin (140 µg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs. Experimental Physiology (2002) 87.1, 41-48.

The vasoregulatory role of nitric oxide (NO) and angiotensin II type 1 (AT1) receptors in the circulation of the submandibular gland (SMG) of rats was studied. The glandular blood flow was determined by means of laser Doppler flowmetry and rubidium isotope technique. The data obtained by these two methods correlated well (r = 0.77; P < 0.01). The AT1 receptor antagonist candesartan (0.5 mg kg-1, I.V.) reduced the vascular resistance in the SMG by 37 % (P < 0.05). By contrast, the NO synthase blocker L-NAME (15 mg kg-1, I.V.) significantly increased vascular resistance in the SMG both in candesartan-treated (P < 0.001) and non-treated (P < 0.001) animals. The increase in resistance was greater (P < 0.05) after previous blockade of AT1 receptors. These findings suggest that the AT1 receptors have an important role in the vasoregulation of the SMG in the rat. As a result of AT1 blockade, NO-dependent tone of glandular vessels may be enhanced significantly. Experimental Physiology (2002) 87.3, 327-333.

The usual model of intermittent hypoxia (sleep apnoea) corresponds to repeated episodes of hypoxia from a few seconds to a few hours interspersed with episodes of normoxia. The aim of this study was to evaluate in rats the effect of two periods of intermittent exposure for 2 months to hypoxia (IHX1, 24 h in hypoxia (428 Torr), 24 h in normoxia; IHX2, 48 h in hypoxia (428 Torr), 24 h in normoxia) as a new model of hypoxia simulating intermittent exposure to high altitude experienced by Andean miners. We assessed the haematological parameters, time course of resting heart rate and systolic blood pressure. We also evaluated the expression of adrenergic and muscarinic receptors. IHX1 and IHX2 produced an increase in haematocrit, haemoglobin concentration and mean corpuscular volume as previously seen in most hypoxic models. IHX1 and IHX2 induced a similar sustained elevation of systolic blood pressure (132 ± 2 and 135 ± 3 mmHg, respectively, vs. the control level of 121 ± 16 mmHg) after 10 days of exposure without change in heart rate. Right ventricular (RV) hypertrophy (225 ± 13 and 268 ± 15 mg g−1, vs. 178 ± 7 mg g−1) and downregulation of α1-adrenoceptor (RV: 127 ± 21 and 94 ± 16 fmol mg−1vs. 157 ± 8 fmol mg−1; left ventricle (LV): 141 ± 5 and 126 ± 9 fmol mg−1vs. 152 ± 5 fmol mg−1) have been found in both groups, with right ventricular hypertrophy being greater and α1-adrenoceptor density being lower in IHX2 than in HX1 groups. These data indicate that both parameters are related to the time of exposure to hypoxia. IHX1 and IHX2 produced the same magnitude of upregulation of muscarinic receptors (LV, 60%; RV, 40%), and no change in β-adrenoceptors. In conclusion, exposure to intermittent hypoxia led to polycythaemia and RV hypertrophy as observed in other types of hypoxia. A specific cardiovascular response was seen, that is an increase in blood pressure without change in heart rate, which was different from the one observed in episodic and chronic hypoxia. Furthermore, this model involved specific modifications of α1-adrenergic and muscarinic expression.

The length of cooperative units along the thin filament of rabbit psoas single muscle fibres was determined by reducing filament length by treatment with the thin filament severing protein, gelsolin, in the presence of Ca2+ and 2,3-butanedione 2-monoxime (BDM). The average time for 50% reduction in isometric tension was 6.7 min at 22°C. The pCa–tension relationship was measured at 22°C, pH 7.00 and ionic strength 200 mM, and the data were fitted to the Hill equation to determine the half-saturation point (K) and the cooperativity (n). Our results demonstrate that the cooperativity does not change much when the remaining isometric tension was in the range 20–100%. The cooperativity quickly diminished when the remaining tension was reduced to less than 20%. Our results further demonstrate that the change in the pK value was minimal and averaged 0.075 (less Ca2+ sensitive) as the thin filament length was reduced. We infer from the first observation that the thin filament cooperativity extends up to 0.2 μm, which includes the maximum of about four basic cooperative units consisting of seven actin molecules, one tropomyosin dimer and one troponin complex. We infer from the second observation that the Ca2+ sensitivity is slightly reduced by removal of the cooperative interaction between neighbouring cooperative units.

The present study was designed to investigate the renal responses to hypotensive haemorrhage early in life and the role of renal sympathetic nerves in modulating these renal responses. To this end, experiments were carried out in conscious, chronically instrumented lambs with either intact renal nerves (n = 7, Intact) or bilateral renal denervation performed at the time of surgery (n = 5, Denervated). Parameters of renal function were measured before and after 20 % haemorrhage (experiment 1) and 0 % haemorrhage (experiment 2), the latter serving as a time control. The two experiments were performed in random order at intervals of 24-48 h. Within 20 min of hypotensive haemorrhage in intact lambs, glomerular filtration rate decreased by ~60 %; this response was not altered by renal denervation. Since renal plasma flow remained constant after haemorrhage, the filtration fraction also decreased. After 20 % haemorrhage, urinary flow rate decreased in intact lambs; this response was also not altered by renal denervation. Excretion rates of Na+ and K+ as well as urinary osmolality and free water clearance were not altered by haemorrhage in either intact or denervated lambs. These data provide the first description of renal responses to haemorrhage early in life. In addition, the present findings provide new information that renal responses to haemorrhage early in life do not appear to be modulated by renal sympathetic nerves. Experimental Physiology (2002) 87.5, 557-562.

The renal medulla contains more mRNA of the inducible isoform of nitric oxide synthase (iNOS) than the cortex, which may be important in preventing ischaemic injury, since blood flow and tissue oxygen tension are normally low in this region. We examined the effects of the bacterial endotoxin E. coli lipopolysaccharide (LPS) on renal function and regional expression of iNOS in male Sprague-Dawley rats. In six rats, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 0.95 ± 0.09 ml min-1 g-1 and 3.36 ± 0.20 ml min-1 g-1, respectively, and decreased significantly to 0.35 ± 0.09 and 1.74 ± 0.54 ml min-1 g-1, respectively, 1 h after administration of LPS. In an additional seven rats, GFR and ERPF were 0.91 ± 0.07 and 2.97 ± 0.30 ml min-1 g-1, respectively, 18 h after LPS administration; these values were similar to those in control rats. In all rats, arterial pressure was stable throughout all study periods. In control rats, immunoblot analysis revealed expression of the iNOS protein in the cortex and more pronounced expression in the medulla. In rats studied 18 h after LPS treatment, there was a striking increase in the iNOS expression in the outer medulla. Immunohistochemical examination in the LPS-treated rats showed limited iNOS immunostaining in the cortex, localised to the vascular endothelium and macula densa; however, intense and widespread staining was noted in the tubular and vascular structures of the outer medulla. These findings demonstrated a differential constitutive expression of iNOS protein in different regions of the rat kidney, and marked augmentation of iNOS expression in the outer medulla by LPS. Experimental Physiology (2002) 87.2, 153-162.

The effects of neuronal inhibition of nitric oxide (NO) production on the bradycardia resulting from stimulation of preganglionic and postganglionic parasympathetic fibres were investigated in an anaesthetised dog preparation following transection of the cervical vagi and in the presence of a β-adrenoreceptor antagonist. Injection of 1-(2-trifluoromethylphenyl) imidazole (TRIM), an inhibitor of neuronally released NO, into the sinus node artery reduced the bradycardia evoked by right cervical vagal stimulation. In contrast, when the response to preganglionic stimulation had been abolished by hexamethonium (10 mg kg-1), the bradycardia following stimulation of postganglionic parasympathetic fibres on the atrial epicardium was unaffected by TRIM. First, these results confirm the facilitatory actions of neuronally released NO on vagal heart responses in the dog. Second, they indicate that this modulatory and facilitatory role of NO is likely to be exerted at vagal preganglionic-postganglionic synaptic mechanisms in the cardiac parasympathetic ganglia and not at the postganglionic-sinoatrial node synapse. Experimental Physiology (2002) 87.1, 49-52.

The purpose of the study was to investigate whether jaw reflexes evoked by selective stimulation of periodontal ligament mechanoreceptors are susceptible to modulation by remote noxious stimulation. Experiments were performed on 10 volunteer subjects. Skin surface recordings were made from the jaw-closing masseter muscle. The subjects activated the muscle to approximately 10% of maximum by biting on a rubber impression of their molar teeth while they received visual feedback of the electromyogram (EMG) of the muscle. Reflexes were produced by the application of gentle mechanical stimuli to an upper central incisor tooth. The stimuli were in the form of ‘ramp and hold’ forces with a 5 ms rise-time and a 1.5 N plateau which lasted 350ms. The resulting reflexes were recorded both under control conditions and while the subjects received a remote noxious stimulus (immersion of a hand in water at 3°C). In all 10 subjects, the stimuli produced a single period of inhibition of masseteric activity (latency, 12.8±0.4 ms; duration, 18.1±1.3 ms; means ± S.E.M.), which was usually followed by a period of increased masseteric activity. The period of inhibition constituted a downward wave in full-wave rectified, averaged signals. The integrals of such waves were significantly smaller (by 17±6.5 %; P = 0.027; Student's t test) when the reflex was evoked during remote noxious stimulation rather than under control conditions. As such reflexes are believed to play a modulatory role during normal oral function, this finding may be relevant to disorders of mastication associated with pain.

This investigation tested the hypothesis that the effects of nitric oxide synthase on myocardial capillary perfusion were reduced during myocardial stunning. Anaesthetized open-chest rabbits were assigned to either a control group or a group treated with a nitric oxide synthase inhibitor. To induce myocardial stunning, a coronary artery was occluded (for 15 min) and then reperfused (for 15 min) twice. During reperfusion, rabbits were given either saline or NG-nitro-L-arginine methyl ester (L-NAME, 30 mg kg-1) followed by I.V. injection of 150 mg kg-1 fluorescein isothiocyanate (FITC)-labelled dextran (molecular weight, 150 000) for 14 s. Fluorescence microscopy was used to identify the perfused vessels and an alkaline phosphatase stain was used to locate the total microvasculature. The 'closest-individual' method was used to estimate the geometric distribution of capillaries. No significant differences were observed in the total volume fraction (mm3 of capillaries per mm3 of tissue) between the control and stunned regions in either the saline- (0.045 ± 0.008 and 0.042 ± 0.009, respectively) or the L-NAME-treated hearts (0.060 ± 0.010 and 0.049 ± 0.005, respectively). There were no significant differences in the percentage volume fraction of perfused capillaries between the control and the stunned regions (49 ± 4 % and 54 ± 4 %, respectively) in saline-treated hearts. In hearts treated with L-NAME, the percentage of perfused capillaries was significantly reduced. The reduction was significantly greater in the control region (~27 %) than the stunned region (~17 %). Closest-individual analysis of the perfused capillary distribution in both groups demonstrated a similar unchanged distribution. Thus, nitric oxide synthase is an important regulator of basal coronary capillary perfusion, and its effects are significantly reduced by myocardial stunning. Experimental Physiology (2002) 87.3, 335-342.

Arterially perfused, decerebrate preparations of the insectivore, Suncus murinus were made to determine whether the emetic reflex could be activated in such a preparation using a range of stimuli shown to be emetic in conscious or anaesthetised Suncus. Efferent phrenic and vagus nerve activities and electromyograms (EMGs) from the temporalis, abdominal oesophagus and trapezius muscles were recorded, as well as longitudinal shortening of the oesophagus and dorso-ventral movements of the thorax. The preparations swallowed spontaneously every 0.6 to 6.5 min. The duration of a swallow was 3.1 ± 0.3 s (recorded as the time taken for the oesophagus to shorten and recover to its resting position) and the oesophagus shortened by 3.5 ± 0.4 mm during a swallow. The emetic reflex was activated by electrical stimulation (30 Hz, 10-20 V, 0.2 ms pulse width, for 30 s) of abdominal vagal afferents (latency < 30 s) or by arterial perfusion with either 40 nM of the capsaicin analogue resiniferatoxin (latency 1.7 ± 0.6 min), 6 µM nicotine (latency 1.6 ± 0.1 min) or 1 µM of the phosphodiesterase IV inhibitor CP-80,633 (latency 8.9 ± 3.9 min). These emetic stimuli produced somatic and visceral movements in Suncus preparations indicative of activation of the emetic reflex. There were pronounced contractions of the thorax that occurred simultaneously with oesophageal shortening and mouth opening, separated by thorax expansion and a burst of phrenic nerve activity. During emetic-like episodes, oesophageal shortenings were only 0.84 ± 0.1 s in duration, faster than the duration of shortening observed during swallowing (cf. swallowing, 3.1 ± 0.3 s; P < 0.0001). The shortening of the oesophagus during emetic-like episodes was 6.2 ± 0.4 mm, which was greater than the shortening seen during swallowing (cf. swallowing, 3.5 ± 0.4 mm; P < 0.0001). We conclude that the emetic reflex can be activated in our Suncus preparations and that this non-sentient small adult animal model can now be used to study the neurophysiology and pharmacology of swallowing and emesis. Experimental Physiology (2002) 87.5, 563-574.