Analysis of the effects of graded levels of hypoxia on noradrenaline-evoked contraction in the rat iliac artery in vitro

Abstract

In rings of rat iliac artery, contractions were evoked by noradrenaline (NA), the selective α₁ adrenoceptor agonist phenylephrine (PE), and K⁺, which causes depolarisation-induced contraction. There was no evidence of α₂ adrenoceptor-evoked contraction. Hypoxia, induced by reducing P_O2 in the bath from 100 mmHg to 70, 55 or 40 mmHg, had similar effects on rings with (E+) and without (E-) endothelium. In E- rings, the NA concentration-response curve was biphasic, whereas that for PE was monophasic. Hypoxia reduced maximum contractions in response to NA and PE (NA_max and PE_max, respectively) without affecting the concentrations that evoked 50 % of maximum contraction (EC₅₀). At P_O2 of 70 mmHg, NA_max of the high affinity α₁ receptor for NA (NA_maxh) and PE_max were reduced by ~15 %, but at P_O2 of 55 and 40 mmHg, NA_maxh was severely attenuated while PE_max fell by 45 and 75 %, respectively. Similarly, the Ca²⁺ channel blocker nicardipine depressed NA_maxh and PE_max, but P_O2 of 55 mmHg further reduced NA_max and PE_max. Hypoxia also reduced contractions evoked by NA, PE or K⁺ at the concentrations required to produce 80 % of the maximum contraction (EC₈₀), receptor-mediated contractions being more affected. Ca²⁺-free conditions reduced the contractions evoked by NA and PE, at the EC₈₀, to ~10 % of control. The K⁺ channel inhibitors glibenclamide and tetraethylammonium did not prevent hypoxia-induced depression of PE-evoked contraction. Thus, contractions evoked in iliac artery by the high affinity subtype of α₁ adrenoceptor for NA, which may respond to circulating levels of NA, and by the single α₁ adrenoceptor subtype for PE, are especially vulnerable to P_O2 levels ≤ 55 mmHg. We propose that this reflects hypoxia-induced inhibition of Ca²⁺ influx through L-type and receptor-operated Ca²⁺ channels; K⁺ channel opening makes little contribution. Experimental Physiology (2002) 87.2, 171-184.