title: Sympathetic modulation of renal blood flow by rilmenidine and captopril: central vs. peripheral effects.
abstract: Renal blood flow (RBF) is modulated by renal sympathetic nerve activity (RSNA). However, agents that are supposed to reduce sympathetic tone, such as rilmenidine and captopril, influence RBF also by direct arteriolar effects. The present study was designed to test to what extent the renal nerves contribute to the renal hemodynamic response to rilmenidine and captopril. We used a technique that allows simultaneous recording of RBF and RSNA to the same kidney in conscious rabbits. We compared the dose-dependent effects of rilmenidine (0.01-1 mg/kg) and captopril (0.03-3 mg/kg) on RBF and RSNA in intact and renal denervated (RNX) rabbits. Because rilmenidine and captopril lower blood pressure, studies were also performed in sinoaortically denervated (SAD) rabbits to determine the role of the baroreflex in the renal hemodynamic response. Rilmenidine reduced arterial pressure, RBF, and RSNA dose dependently. In intact rabbits (n = 10), renal conductance (RC) remained unaltered (3 +/- 5%), even after the 1-mg/kg dose, which completely abolished RSNA. In RNX rabbits (n = 6), RC fell by 18 +/- 5%, whereas in SAD rabbits (n = 7) RC increased by 30 +/- 20% after rilmenidine. In intact rabbits, captopril increased RSNA maximally by 64 +/- 8%. RSNA did not rise in SAD rabbits. Despite the differential response or absence of RSNA, captopril increased RC to a comparable degree (maximally 40-50%) in all three groups. Using spectral analysis techniques, we found that in all groups, independently of ongoing RSNA, captopril, but not rilmenidine, attenuated both myogenic (0.07-0.25 Hz) and tubuloglomerular feedback (0.01-0.07 Hz) related fluctuations in RC. We conclude that, in conscious rabbits, the renal vasodilator effect of rilmenidine depends on the level of ongoing RSNA. Its sympatholytic effect is, however, blunted by a direct arteriolar vasoconstrictor effect. In contrast, the renal vasodilator effect of captopril is not modulated by ongoing RSNA and is associated with impairment of autoregulation of RBF.
authors.affiliation: Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, 6200 MD Maastricht, The Netherlands. b.janssen@farmaco.unimaas.nl
authors.forename: Ben J A
authors.initials: BJ
authors.lastname: Janssen
authors.forename: Elena V
authors.initials: EV
authors.lastname: Lukoshkova
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D005246:Feedback / Q000502:physiology; D005260:Female; D007678:Kidney Glomerulus / Q000098:blood supply / Q000294:innervation / Q000502:physiology; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D011817:Rabbits; D012079:Renal Circulation / Q000502:physiology*; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D010080:Oxazoles; D002216:Captopril; D000077769:Rilmenidine