title: Development of adrenergic and nonadrenergic pressor mechanisms in rats sympathectomized from birth.
abstract: Rats were sympathectomized by administering guanethidine from birth through 50 days of age. Experiments were performed in vivo under anesthesia at 18, 25, 40, 60, 70 and 100 days of age to determine if sympathectomy (SNX) attenuated development of vascular noradrenergic contraction and the mechanisms that support mean arterial blood pressure (MAP) after SNX. The maximum and ED50 of the pressor response to the alpha-1 noradrenergic agonist methoxamine was used to test contractility. MAP support mechanisms were assessed indirectly by measuring hypotensive responses to sequential interventions: adrenalectomy, chlorisondamine (ganglionic blockade), phentolamine (alpha-1 and alpha-2 noradrenergic blockade), angiotensin II antagonist, arginine vasopressin antagonist and hydralazine (direct acting vasodilator). Guanethidine abolished the pressor response to tyramine-evoked norepinephrine release, decreased plasma norepinephrine 70% without change in epinephrine and decreased methoxamine ED50. Maxima of methoxamine pressor responses were comparable in sympathectomized rats and controls at all ages. Resting MAP was 7 to 20% lower in sympathectomized rats, but MAP after eliminating autonomic nerve influences was 27 to 36% higher. SNX abolished hypotensive responses to chlorisondamine and decreased responses to phentolamine. In contrast, there were increased responses to angiotensin II antagonist (70-240%), arginine vasopressin antagonist (250%) and hydralazine (50-300%). SNX did not change MAP measured after maximum dilation with hydralazine. We conclude that in rats sympathectomized from birth vascular noradrenergic contraction and intrinsic resistance develop normally, blood pressure is independent of circulating catecholamines from the adrenal or other sources although the vasculature is supersensitive and blood pressure support depends on an enhanced pressor influence of nonadrenergic vasoactive substances including angiotensin II and arginine vasopressin.
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001127:Arginine Vasopressin / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D002714:Chlorisondamine / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008729:Methoxamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D002395:Catecholamines; D000804:Angiotensin II; D001127:Arginine Vasopressin; D008729:Methoxamine; D002714:Chlorisondamine; D006145:Guanethidine