title: Effects of Ca(2+) channel activity on renal hemodynamics during acute attenuation of NO synthesis in the rat.
abstract: In cultured vascular muscle cells, nitric oxide (NO) has been shown to inhibit voltage-dependent Ca(2+) channels, which are involved in renal blood flow (RBF) autoregulation. Therefore, our purpose was to specify in vivo the effects of this interaction on RBF autoregulation. To do so, hemodynamics were investigated in anesthetized rats during Ca(2+) channel blockade before or after acute NO synthesis inhibition. Rats were treated intravenously with vehicle (n = 10), 0.3 mg/kg body wt N(G)-nitro-L-arginine-methyl ester (L-NAME; n = 7), 4.5 microg. kg body wt(-1). min(-1) nifedipine (n = 8) alone, or with nifedipine infused before (n = 8), after (n = 8), or coadministered with L-NAME (n = 10). Baseline renal vascular resistance (RVR) averaged 14.0 +/- 1.2 resistance units and did not change after vehicle. RVR increased or decreased significantly by 27 and 29% after L-NAME or nifedipine, respectively. Nifedipine reversed, but did not prevent, RVR increase after or coadministered with L-NAME. RBF autoregulation was maintained after L-NAME, but the autoregulatory pressure limit (P(A)) was significantly lowered by 15 mmHg. Nifedipine pretreatment or coadministration with L-NAME limited P(A) resetting or suppressed autoregulation at higher doses. Results were similar with verapamil. Intrarenal blockade of Ca(2+)-activated K(+) channels also prevented autoregulatory resetting by L-NAME (n = 8). These findings suggest NO inhibits voltage-dependent Ca(2+) channels and thereby modulates RBF autoregulatory efficiency.
authors.affiliation: Service de Physiologie et Pharmacologie, Faculté de Médecine et de Pharmacie, Université de Mons-Hainaut, 7000 Mons, Belgium. Ronald.Kramp@umh.ac.be
authors.forename: R A
authors.initials: RA
authors.lastname: Kramp
authors.forename: P
authors.initials: P
authors.lastname: Fourmanoir
authors.forename: L
authors.initials: L
authors.lastname: Ladrière
authors.forename: E
authors.initials: E
authors.lastname: Joly
authors.forename: C
authors.initials: C
authors.lastname: Gerbaux
authors.forename: A
authors.initials: A
authors.lastname: El Hajjam
authors.forename: N
authors.initials: N
authors.lastname: Caron
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D017942:Nitric Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D017942:Nitric Acid; D009543:Nifedipine; D019331:NG-Nitroarginine Methyl Ester