Summary
The effect of functional impairment of the renin-angiotensin system on the vasoconstriction mediated by postsynaptic α1 and α2-adrenoceptors in pithed normotensive rats was studied. Selective α1-adrenoceptor stimulation was induced by intravenously administered cirazoline, whereas B-HT 920 was used as a selective agonists at α2-adrenoceptors. The angiotensin converting enzyme was inhibited by intravenous treatment of the pithed rats with captopril, teprotide or enalapril. Blockade of angiotensin receptors was produced by intravenously applied [Sar1 Ala8]angiotensin II (saralasin). Pretreatment with angiotensin converting enzyme inhibitors or with saralasin in doses which produced a maximal reduction in basal diastolic blood pressure, only slightly attenuated the hypertensive response to cirazoline. In contrast, these drugs provoked a most significant reduction of the α2-adrenoceptor mediated vasoconstriction. Restoration of the basal diastolic blood pressure by intravenous infusion with angiotensin II or with vasopressin completely reversed the inhibitory effect of captopril on the vasopressor response to B-HT 920. One hour after bilateral nephrectomy, captopril still reduced the α2-adrenoceptor mediated vasoconstriction. However, 18–24 h after bilateral nephrectomy, captopril had no additional inhibitory effect on the vasopressor response to selective α2-adrenoceptor stimulation. It is concluded that in pithed normotensive rats the pressor response to α2-adrenoceptor stimulation is significantly potentiated by endogenous angiotensin II, even at low circulating levels of the octapeptide. The modulatory action of angiotensin II on the α-adrenoceptor mediated vasoconstriction probably represents an effect on the basal arteriolar muscular tone rather than a specific interaction.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
De Jonge A, Wilffert B, Kalkman HO, Van Meel JCA, Thoolen MJMC, Timmermans PBMWM, Van Zwieten PA (1981) Captopril impairs the vascular smooth muscle contraction mediated by postsynaptic α2-adrenoceptors in the pithed normotensive rat. Eur J Pharmacol 74:385–386
Engel SL, Schaeffer TR, Gold BI, Rubin R (1972) Inhibition of pressor effects of angiotensin I and augmentation of the depressor effects of bradykinin by synthetic peptides (36433). Proc Soc Exp Biol Med 140:240–244
Ferreira SH (1965) A bradykinin-potentiating factor (BPF) present in the venom of bothrops jararaca. Br J Pharmacol 24: 163–169
Hatton R, Clough DP (1982) Captopril interferes with neurogenic vasoconstriction in the pithed rat by angiotensin dependent mechanisms. J Cardiovasc Pharmacol 4: 116–123
Johnson EM, Marshall GR, Needleman P (1974) Modification of responses to sympathetic nerve stimulation by the renin-angiotensin system in rats. Br J Pharmacol 51: 541–547
Kobinger W, Pichler L (1980) Investigations into different types of post-and presynaptic α-adrenoceptors at cardiovascular sites in rats. Eur J Pharmacol 65: 393–402
Peach MJ (1977) Renin-angiotensin system: biochemistry and mechanisms of action. Physiol Rev 57: 313–370
Redleaf PD, Tobian L (1958) The question of vascular hyper-responsiveness in hypertension. Circ Res 6: 185–193
Starke K (1981) α-Adrenoceptor subclassification. Rev Physiol Biochem Pharmacol 88: 199–236
Timmermans PBMWM, Van Zwieten PA (1981) The postsynaptic α2-adrenoceptor. J Auton Pharmacol 1: 171–183
Van Meel JCA, De Jonge A, Timmermans PBMWM, Van Zwieten PA (1981) Selectivity of some α-adrenoceptor agonists for peripheral α1- and α2-adrenoceptors in the normotensive rat. J Pharmacol Exp Ther 219: 760–767
Wallenstein S, Zucker CL, Fleiss JL (1980) Some statistical methods usefull in circulation research. Circ Res 47: 1–9
Westfall ThC (1977) Local regulation of adrenergic neurotransmission. Physiol Rev 57: 659–728
Zimmerman BG (1981) Adrenergic facilitation by angiotensin: does it serve a physiological function? Clin Sci 60: 343–348
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
de Jonge, A., Knape, J.T.A., van Meel, J.C.A. et al. Effect of converting enzyme inhibition and angiotensin receptor blockade on the vasoconstriction mediated by α1 and α2 stimulation in pithed normotensive rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 321, 309–313 (1982). https://doi.org/10.1007/BF00498519
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00498519