Losartan inhibits sympathetic and cardiovascular responses to carotid occlusion

Kumagai, K.; Reid, I. A.

We have reported that inhibition of angiotensin-converting enzyme with captopril attenuates the cardiovascular responses to bilateral carotid occlusion in conscious rabbits and proposed that the attenuation results from removal of a facilitatory action of angiotensin II on the sympathetic nervous system. The aim of the present study was to assess the effect of carotid occlusion on renal sympathetic nerve activity in conscious rabbits and to investigate the effect of the angiotensin II subtype 1 (AT-1) receptor antagonist losartan on the cardiovascular and renal sympathetic nerve activity responses to carotid occlusion. In seven conscious, aortic depressor nerve-sectioned rabbits, carotid occlusion elicited prompt and reproducible increases in mean arterial pressure from 75+-2 to 124+-5 mmHg (P lt .001), heart rate from 285+-8 to 317+-9 beats per minute (P lt .01), and renal sympathetic nerve activity to 165+-11% of control (P lt .01). In the same rabbits, losartan (5 mg/kg IV) decreased mean arterial pressure by 9+-2 mm Hg (P lt .01), increased renal sympathetic nerve activity to 143+-13% of control (P lt .05), but did not alter heart rate. Losartan significantly attenuated (P lt .01) the mean arterial pressure (66+-2 to 81+-2 mm Hg), heart rate (282+-9 to 289+-7 beats per minute), and renal sympathetic nerve activity (143+-13% to 159+-15% of control) responses to carotid occlusion. The responses to carotid occlusion were not restored when the hypotension produced by losartan was reversed by phenylephrine infusion, and nitroprusside-induced hypotension did not attenuate the pressor or renal sympathetic nerve activity responses to carotid occlusion. These results provide evidence that endogenous angiotensin II facilitates the cardiovascular and sympathetic nerve activity responses to carotid occlusion by an action on central AT-1 receptors.