Summary
The cardiovascular effects of angiotensin II were examined in aortic blood pressure-controlled and-uncontrolled pithed rats. Angiotensin II induced a dose-dependent increase in diastolic blood pressure, left ventricular pressure (LVP), dP/dt (the first derivative of LVP) and heart rate in pithed rats. The maximal responses for these parameters were similar to those to noradrenaline, except for the rise in diastolic blood pressure, where noradrenaline caused a greater increase than angiotensin II. After treatment with propranolol, the positive chronotropic effect of angiotensin II was abolished. Angiotensin II produced a dose-dependent increase in diastolic blood pressure, which was similar to that of vasopressin, and an increase in dP/dtmax, which proved much greater than that of vasopressin. When aortic blood pressure was controlled and the β-receptors were blocked by propranolol, angiotensin II caused a dose-dependent increase in dP/dtmax without affecting the left ventricular enddiastolic pressure. The same results were obtained after both β- and α-adrenoceptors were blocked by propranolol and phentolamine. Losartan but not PD 123177 caused parallel rightward shifts of the dose-response curve of angiotensin II for dP/dtmax in the aortic blood pressure controlled pithed rat without altering the maximal response. It is concluded that in the pithed rat angiotensin II produced an increase in myocardial contractile force which is not mediated by β- or α-adrenoceptors. The inotropic effect appears to be mediated by angiotensin receptors, of the AT1-subtype.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baker KM, Booz GW, Dostal DE (1992) Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. Annu Rev Physiol 54:227–241
Buccafusco JJ, Serra M (1985) Role of cholinergic neurons in the cardiovascular responses evoked by central injection of bradykinin or angiotensin II in conscious rats. Eur J Pharmacol 113:43–51
Chang RS, Lotti VJ (1991) Angiotensin receptor subtypes in rat, rabbit and monkey tissues: relative distribution and species dependency. Life Sci 49:1485–1490
Decker N, Ehrhardt JD, Leclerc G, Schwartz J (1984) Postjunctional α-adrenoceptors α1 and α2 subtypes in vasculature in vitro and in vivo. Naunyn-Schmiedeberg's Arch Pharmacol 326:1–6
Doggrell SA (1989) The effects of atriopeptin and angiotensin on the rat right ventricle. Gen Pharmacol 20:253–257
Dostal DE, Baker KM (1992) Angiotensin II stimulation of left ventricular hypertrophy in adult rat heart. Am J Hypertens 5 (5 PT 1):276–280
Dowell RT (1991) Comprehensive evaluation of cardiovascular function in the anaesthetized rat. Methods Find Exp Clin Pharmacol 13:609–616
Einstein R, Mihailidou AS, Richardson DP (1987) Positive inotropic effects of histamine in anaesthetized dogs. Br J Pharmac 92:445–450
Ferrario CM, Gildenberg PL, Mccubbin JW (1972) Cardiovascular effects of angiotensin mediated by the central nervous system. Circ Res 30:257–262
Knape JTA, van Zwieten PA (1988) Positive chronotropic activity of angiotensin 11 in the pithed normotensive rat is primarily due to activation of cardiac β1-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 338:185–190
Kopp SJ (1983) Vascular intracardiac catheterization technique for multiphasic evaluation of rat heart in vivo. Toxicol Appl Pharmacol 70:273–282
Lee WG, Ismay MI, Lumbers ER (1980) Mechanisms by which angiotensin II affects the heart rate of the conscious sheep. Circ Res 47:286–292
Mason DT (1969) Usefulness and limitations of the rate of rise of intraventricular pressure (dP/dt) in the evaluation of myocardial contractility in man. Am J Cardiol 23:516–527
Neyses L, Vetter H (1989) Action of atrial natriuretic peptide and angiotensin II on the myocardium: Studies in isolated rat ventricular cardiomyocytes. Biochem Biophys Res Commun 163:1435–1443
Penny WJ, Culling W Lewis MJ, Sheridan DJ (1985) Antiarrhythmic and electrophysiological effects of alpha-adrenoceptor blockade during myocardial ischaemia and reperfusion in isolated guinea-pig heart. J Mol Cell Cardiol 17:399–409
Rogers TB, Gaa ST, Allen IS (1986) Identification and characterization of functional angiotensin II receptors on cultured heart myocytes. J Pharmacol Exp Ther 236:438–444
Saito K, Gutkind JS, Saavedra JM (1987) Angiotensin II binding sites in the conduction system of rat hearts. Am J Physiol 253:H1618–1622
Sechi LA, Grady EF, Griffin CA, Kalinyak JE, Schambelan M (1991) Characterization of angiotensin II receptor subtypes in the rat kidney and heart using the non-peptide antagonists DuP 753 and PD 123177. J Hypertens 9:S224–225
Steinfath M, Chen YY, Lavicky J, Magnussen O, Nose M, Rosswag S, Schmitz W, Scholz H (1992) Cardiac α1-adrenoceptor densities in different mammalian species. Br J Pharmacol 107:185–188
Vollmer RS, Meyers-Schoy SA, Marinelli RR (1991) Mechanisms involved in angiotensin II induced increases in cardiac output in pithed rats. Clin Exp Hypertens 13:1433–1445
Wong PC, Hart SD, Zaspel AM, Chiu AT, Ardecky RJ, Smith RD, Timmermans PMWM (1990) Functional studies of angiotensin II receptor subtype-specific ligands: DuP 753 (All-1) and PD 123177 (All-2). J Pharmacol Exp Ther 255:584–592
Yamada S, Ishima T, Tomita T, Hayashi M, Okada T, Hayashi E (1984) Alterations in cardiac alpha- and beta-adrenoceptors during the development of spontaneous hypertension. J Pharmacol Exp Ther 228:454–460
Zimmer H-G (1983) Measurement of left ventricular hemodynamic parameters in closed-chest rats under control and various pathophysiologic conditions. Basic Res Cardiol 78:77–84
Author information
Authors and Affiliations
Additional information
Correspondence to J. Zhang at the above address
Rights and permissions
About this article
Cite this article
Zhang, J., Pfaffendorf, M. & van Zwieten, P. Positive inotropic action of angiotensin II in the pithed rat. Naunyn-Schmiedeberg's Arch Pharmacol 347, 658–663 (1993). https://doi.org/10.1007/BF00166950
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00166950