Positive inotropic action of angiotensin II in the pithed rat

Abstract

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 beta-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 beta- and alpha-adrenoceptors were blocked by propranolol and phentolamine. Losartan but not PD123177 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 beta- or alpha-adrenoceptors. The inotropic effect appears to be mediated by angiotensin receptors, of the AT1-subtype.

Direct positive chronotropic effects of angiotensin II and angiotensin III in pithed rats and in rat isolated atria

“…It has been demonstrated that All can cause positive inotropic effects in rats (Zhang et al, 1993) and other species (Lindpaintner & Garten, 1991). However, in isolated right atria preparations, we observed that All, AIII and AIV slightly decreased the amplitude of beating simultaneously with the increases in frequency.…”

“…Previous investigations in our department (Knape & van Zwieten, 1988;Zhang et al, 1993) have shown that the tachycardic response induced by All in the pithed rat is generated by a direct positive chronotropic effect as well as by an indirect action of All, which is known to stimulate the sympathetic ganglia, thus leading to the release of catecholamines. It has also been found (Allen et al, 1988) that All increases the spontaneous contractile frequency in cultured heart myocytes from neonatal rats.…”

Potential Mechanisms Involved in Palmitoylethanolamide-Induced Vasodepressor Effects in Rats

“…In this respect, one possibility that this study did not explore is the potential interference of palmitoylethanolamide with the RAAS, in view that in pithed rats a proportion of blood pressure seems to be maintained by activation of the RAAS, as reported by Schlicker et al [30]. Consistent with this possibility, infusions of angiotensin II produce tachycardic and vasopressor responses [33,34]. Clearly, this is a hypothetical speculation that requires other experimental approaches that include the use of i.v.…”

Block of Kv1.7 potassium currents increases glucose‐stimulated insulin secretion

“…Glucose clamp experiments employed the pithed rat preparation, which is well established as a model for peripheral cardiovascular regulation, given that central neural reflex mechanisms have been eliminated (Gillespie & Muir, 1967; Zhang et al, 1993). We used it in order to remove possible direct neural influences on pancreatic function.…”