Role of AT1 receptors and autonomic nervous system in mediating acute presser responses to ANG II in anesthetized mice

Hemodynamic responses to angiotensin IT and the role of AT(1) and AT(2) receptors and the autonomic nervous system in mediating acute responses to angiotensin II were investigated in anesthetized CD1 mice. Injections of angiotensin II caused dose-related increases in systemic arterial pressure that were antagonized by candesartan. Presser responses to angiotensin II were not altered by PD-123,319 in doses up to 25 mg/kg iv. At the lowest dose studied (20 mu g/kg iv), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 mu g/kg iv) the dose-response curve for angiotensin II was shifted to the right in a nonparallel manner with inhibitory effects that could not be surmounted. The inhibitory effects of candesartan were selective and were similar in animals pretreated with enalaprilat (1 mg/kg iv) to reduce endogenous angiotensin II production. Acute presser responses to angiotensin II were not altered by propranolol (200 mu g/kg iv), phentolamine (200 mu g/kg iv), or atropine (1 mg/kg iv) but were enhanced by hexamethonium (5 mg/kg iv). Increases in total peripheral resistance induced by angiotensin II were inhibited by the AT(1)-receptor antagonist but were not altered by AT(2-), alpha-, or beta-receptor antagonists. These results suggest that acute presser responses to angiotensin II are mediated by AT(1) receptors, are buffered by the baroreceptors, and are not modulated by effects on AT(2) receptors and that activation of the sympathetic nervous system plays little if any role in mediating rapid hemodynamic responses to the peptide in anesthetized CD1 mice.