title: Baroreceptor-independent renal nerve inhibition by intracerebroventricular angiotensin II in conscious sheep.
abstract: 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.
authors.affiliation: Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia.
authors.forename: C N
authors.initials: CN
authors.lastname: May
authors.forename: R M
authors.initials: RM
authors.lastname: McAllen
mesh_terms: 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
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D010656:Phenylephrine; D019808:Losartan