Effect of a monoclonal antibody to angiotensin II on hemodynamic responses to noradrenergic stimulation in pithed rats.
A specific angiotensin II monoclonal antibody, KAA8, was used to examine the interaction between sympathetic function and angiotensin II in pithed rats. KAA8, at 5 or 50 mg/kg i.v., did not alter the mean blood pressure, cardiac output, total peripheral resistance, or heart rate responses to sympathetic neural stimulation (0.25-4.0 Hz) or to norepinephrine (0.3-3 micrograms/kg i.v.) but blocked significantly the hemodynamic responses to angiotensin II (0.03-1.0 microgram/kg i.v.) and to angiotensin III (0.3-10 micrograms/kg i.v.). KAA8 treatment also reduced the plasma immunoreactive angiotensin II from 2,880 +/- 475 pg/ml to an undetectable level. In contrast, captopril (5 mg/kg i.v.) and saralasin (10 or 50 micrograms/kg/min i.v.) inhibited the mean blood pressure and total peripheral resistance responses, but not the cardiac output and heart rate responses, to sympathetic neural stimulation and to norepinephrine. These results, which confirm previous findings by Kaufman and Vollmer (Kaufman LJ, Vollmer RR: Endogenous angiotensin II facilitates sympathetically mediated hemodynamic responses in pithed rats. J Pharmacol Exp Ther 1985;235:128-134), demonstrate that angiotensin II selectively potentiates the sympathetic vascular function in the pithed rat. However, our results suggest that circulating angiotensin II does not appear to interact with the sympathetic vascular function. It is speculated that in the pithed rat the sympathetic vascular response is enhanced by vascular-formed angiotensin II.
Wong
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Medical Products Department, E.I. du Pont de Nemours & Company, Inc., Wilmington, DE 19880-0400.
Reilly
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Timmermans
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D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000502:physiology; D003655:Decerebrate State; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D014667:Vasopressins; D000804:Angiotensin II; D000803:Angiotensin I; D009638:Norepinephrine