Increased vascular responsiveness to α2-adrenergic stimulation during NOS inhibition-induced hypertension.

Increased vascular resistance during systemic nitric oxide synthase (NOS) inhibition is dependent on adrenergic vasoconstriction. This study tested the hypothesis that increased vascular sensitivity to adrenergic agonists contributes to this vasoconstriction. Superior mesenteric arteries and thoracic aortae from male Sprague-Dawley rats drinking water containing N ω-nitro-l-arginine (l-NNA; 14 days, 60 mg ⋅ kg-1 ⋅ day-1) and control rats were cut into helical strips, and endothelium was removed for contractile experiments.l-NNA arteries were more sensitive to UK-14304 (α2-adrenergic agonist) and norepinephrine (NE), whereas responses to phenylephrine (PE) were not different [concentration causing 50% maximal response (EC50),l-NNA vs. control: UK-14304, 0.071 vs. 0.71 μmol/l; NE, 1.15 vs. 9.95 nmol/l]. Yohimbine, an α2-selective antagonist, caused a concentration-dependent inhibition of contraction to NE only inl-NNA arteries (EC50 = 6.3 vs. 1.6 nmol/l at 1 nmol/l yohimbine), whereas prazosin shifted NE curves similarly in arteries from both groups. Yohimbine (10 nmol/l) inhibited contractions to UK-14304 (EC50 = 59 μmol/l vs. 17 μmol/l) but not contractions to PE, whereas prazosin inhibited both. These data indicate thatl-NNA-induced hypertension leads to increased sensitivity of prazosin-sensitive α2-adrenoceptors, an upregulation that could cause the increased vasoconstrictor response to NE in this model of hypertension.