Baroreceptor-independent renal nerve inhibition by intracerebroventricular angiotensin II in conscious sheep.
The effect of central administration of angiotensin II (ANG II) on efferent renal sympathetic nerve activity (RSNA) was studied in conscious sheep. ANG II (1 nmol/h), infused for 30 min into the lateral cerebral ventricles in five sheep, did not alter mean arterial pressure (MAP) but reduced RSNA to 38 +/- 5% of control. Intracerebroventricular infusion of higher doses of ANG II (3 and 10 nmol/h), which increased MAP by 12 +/- 2 and 14 +/- 3 mmHg, respectively, reduced RSNA to 9 +/- 5 and 11 +/- 7% of control. MAP and RSNA gradually returned to control over a period of 2 h after the infusions. Intracerebroventricular losartan (1 mg/h for 1 h before, and then during, angiotensin infusion) blocked all the effects of angiotensin (3 nmol/h). Baroreflex relationships constructed from the beat-to-beat relationship of RSNA to diastolic pressure showed a significant leftward shift during intracerebroventricular ANG II compared with the control relationship. The beat-to-beat relationship between central venous pressure and RSNA was abolished during intracerebroventricular infusion of ANG II. These findings demonstrate that intracerebroventricular ANG II has a direct central inhibitory action on RSNA that is independent of both arterial and low-pressure baroreceptors. This effect of angiotensin is mediated by central angiotensin AT-1 receptors.
May
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Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia.
McAllen
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RM
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002496:Central Venous Pressure / Q000187:drug effects; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation*; D019808:Losartan; D009433:Neural Inhibition; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology*; D012756:Sheep; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D010656:Phenylephrine; D019808:Losartan