Hypertension during chronic peripheral and central infusion of angiotensin III.
Recent studies have suggested that the angiotensin II (ANG II) metabolite [Des-Asp]ANG II (ANG III) may be nearly equipotent with the parent compound in causing several acute neural responses known to be stimulated by angiotensin peptides (i.e., drinking, augmentation of sympathetic neurotransmission, and centrally mediated pressor responses). Because neural actions of ANG II are thought to contribute importantly to the ability of this hormone to cause chronic hypertension, the purpose of the present experiments was to explore the cardiovascular effects of chronic administration of ANG III either into the bloodstream or directly into the brain via the cerebral ventricles. The neurogenic component of the pressor response to acute infusion of ANG III also was reinvestigated. In anesthetized pithed rats (n = 6) ANG III had only 10% of the pressor potency of ANG II when given by acute (5-10 min) intravenous infusion. In conscious rats (n = 5) ANG III had 25% of the pressor potency of ANG II when tested using acute intravenous administration. The acute intravenous pressor potency ratio in conscious versus pithed rats was 4.8 for ANG III and 1.1 for ANG II, suggesting that, compared with ANG II, the pressor response to ANG III shows a greater dependence on neurogenic mechanisms at the doses tested. Chronic (5-day) intravenous infusion of ANG III (at 10, 20, and 100 ng/min) caused sustained hypertension without changes in fluid/electrolyte balance, but only at a dose (100 ng/min) estimated to produce blood levels of ANG III well beyond the "physiological" range.(ABSTRACT TRUNCATED AT 250 WORDS)
D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000805:Angiotensin III / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D006439:Hemodynamics / Q000187:drug effects; D007263:Infusions, Parenteral; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000804:Angiotensin II; D000805:Angiotensin III