Alterations in cardiovascular responsiveness and adrenoceptor binding during catecholamine infusion hypertension in rats.
Chronic continuous infusion of norepinephrine in rats causes alterations in biochemical and physiologic responses of the cardiovascular system and in cardiovascular adrenoceptor number. The response of cardiac and aortic ornithine decarboxylase (ODC) activity to stimulation by norepinephrine was decreased in rats receiving norepinephrine infusion. These responses are due to stimulation of beta- and alpha-adrenergic receptors, respectively. Additionally, there was reduced stimulation of aortic ODC activity by angiotensin II and vasopressin. The cardiac ODC response to angiotensin II was decreased, but the response to vasopressin was not affected. The decreased ODC response is accompanied by decreased pressor responses to the alpha-adrenergic agonist phenylephrine. Decreased numbers of alpha- and beta-adrenoceptor binding sites (as measured by the binding of [3H]prazosin and [125I]pindolol) might mediate, in part, the altered responses to adrenergic agonists. The decreased cardiovascular responsiveness measured in these animals after several days of norepinephrine infusion hypertension contrasts with the increased responses found in most other forms of hypertension. This provides a useful model in which to examine the consequences of prolonged adrenergic receptor stimulation.
Johnson
M D
MD
Department of Pharmacology, Medical College of Pennsylvania/Eastern Pennsylvania Psychiatric Institute, Philadelphia 19129.
McMillian
M K
MK
Schanberg
S M
SM
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010869:Pindolol / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; D001127:Arginine Vasopressin; D010869:Pindolol; D009955:Ornithine Decarboxylase; D009638:Norepinephrine; D011224:Prazosin