Regional blood flows and cardiac function changes induced by angiotensin II in conscious dogs
Doursout, M.F.; Chelly, J.E.; Hartley, C.J.; Szilagyi, J.; Montastruc, J.L.; Buckley, J.P.
Journal of Pharmacology and Experimental Therapeutics 246(2): 591-596
1988
ISSN/ISBN: 0022-3565 PMID: 2969978 Document Number: 325769
Hemodynamic properties of angiotensin (ANG) II 1, 5, 10 and 100 ng/kg i.v. and 10, 100 and 1000 ng/kg i.v.t. were assessed in conscious dogs. ANG II i.v. produced a dose-dependent pressor response (59 .+-. 5-124 .+-. 16 mmHg) and renal vasoconstriction (1.3 .+-. 0.4-96 .+-. 32 mmHg/ml/min). Ganglionic blockade (chlorisondamine 2 mg/kg i.v.) diminished mean arterial responses without altering peptide effects on renal circulation. At the highest dose, ANG II i.v. induced cardiac stimulation: increased heart rate (75 .+-. 4-115 .+-. 6 beats/min), cardiac output (2.0 .+-. 0.1-2.4 .+-. 0.2 l/min), dP/dt (2308 .+-. 181-2773 .+-. 173 mmHg/sec) and coronary blood flow (49 .+-. 10-96 .+-. 23 ml/min). Although with chlorisondamine cardiac response was more pronounced, subsequent beta blockade abolished it. Concomitantly, an isolated increase in plasma epinephrine was recorded (63 .+-. 8-1505 .+-. 354 pg/ml). A pressor response (59 .+-. 8-89 .+-. 13 mmHg) and renal vasoconstriction (1.1 .+-. 0.1-2.2 .+-. 0.5 mmHg/ml/min) were also produced by ANG II i.v.t. at the highest dose. These centrally mediated changes were prevented by chlorisondamine. Our study demonstrates 1) i.v. ANG II-mediated pressor responses are dependent on direct and indirect components, the relative contribution of each being dependent on the regional circulation; ANG II i.v. also produced biphasic cardiac response-an initial centrally mediated depression and a secondary stimulation dependent on epinephrine via cardiac beta receptors and 2) i.v.t. ANG II-mediated pressor effects are essentially indirect. Finally, no evidence was found to support the role of vasopressin in ANG II effects.