title: Differential contribution of endothelial function to vascular reactivity in conduit and resistance arteries from deoxycorticosterone-salt hypertensive rats.
abstract: The purpose of these studies was to compare changes in conduit and resistance artery function in deoxycorticosterone-salt hypertensive rats. We hypothesized that if there was a common mechanism producing changes in vascular function in hypertension, then there would be similar alterations in reactivity of conduit and resistance arteries. Helically cut strips of common carotid artery were prepared for measurement of isometric force generation, and segments of small mesenteric arteries were pressurized for video dimension analysis. Sensitivity of arteries to phenylephrine and acetylcholine was determined. Carotid arteries from deoxycorticosterone-salt hypertensive rats were more sensitive to phenylephrine than arteries from control rats, whereas mesenteric resistance arteries from hypertensive rats were less sensitive to phenylephrine. In carotid arteries, endothelial denudation or incubation with N psi-nitro-L-arginine increased phenylephrine sensitivity in control rats to the level seen in deoxycorticosterone-salt rats. These manipulations had no effect on phenylephrine sensitivity in arteries from deoxycorticosterone-salt rats. In mesenteric resistance arteries, endothelium denudation normalized the depressed phenylephrine sensitivity in arteries from hypertensive rats but had no effect on arteries from normotensive rats. This depressed phenylephrine sensitivity in deoxycorticosterone-salt mesenteric arteries was not reversed by incubation with Npsi-nitro-L-arginine. Acetylcholine-induced relaxation was depressed in carotid arteries from deoxycorticosterone-salt hypertensive rats, and Npsi-nitro-L-arginine blocked these relaxations. In contrast, acetylcholine relaxation in the mesenteric arteries from normotensive and hypertensive rats did not differ. N psi-nitro-L-arginine slightly but significantly attenuated acetylcholine dilation only in mesenteric resistance arteries from the hypertensive rats. We conclude that qualitatively different changes in vasoconstrictor sensitivity to phenylephrine occur in carotid arteries and mesenteric resistance arteries of deoxycorticosterone-salt hypertensive rats. The increased phenylephrine sensitivity in carotid arteries in this model of hypertension is due to the loss of endothelium-derived nitric oxide production. In contrast, the decreased phenylephrine sensitivity in mesenteric resistance arteries from deoxy-corticosterone-salt rats is due to a non-nitric oxide-mediated influence of the endothelium that is absent in arteries from normotensive rats.
authors.affiliation: Department of Pharmacology and Neuoroscience, Albany Medical College, NY 12208, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: White
authors.forename: C O
authors.initials: CO
authors.lastname: Rivera
authors.forename: C B
authors.initials: CB
authors.lastname: Davison
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D019335:Nitroarginine; D003900:Desoxycorticosterone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine