title: Interactive control of renal function by alpha 2-adrenergic system and nitric oxide: role of angiotensin II.
abstract: We studied the role of angiotensin II (AII) in the interactive control of renal function by the alpha 2-adrenergic system and nitric oxide (NO) in adult male Munich Wistar rats 5-7 days after ipsilateral renal denervation (DNX). Renal micropuncture was used under euvolemic conditions before (period 1) and during (period 2) systemic inhibition of NO synthase (NOS) with NG-monomethyl-L-arginine (L-NMMA) in three groups. Group 1 served as a DNX control. In group 2, the alpha 2-adrenergic agonist B-HT 933 (BHT) was infused systemically throughout the experiment. In group 3, the AII-receptor blocker, Iosartan (LOS), was infused before period 2 as well as throughout infusion of BHT. L-NMMA increased blood pressure (BP) to a similar degree in all three groups. In group 1, infusion of L-NMMA did not affect glomerular hemodynamics or tubular function. With BHT in group 2, L-NMMA reduced absolute proximal tubular reabsorption (APR) and by reducing nephron plasma flow (SNPF) and glomerular ultrafiltration coefficient (LpA) caused nephron filtration rate (SNGFR) to decrease, a response described in innervated kidneys. LOS in group 3 abrogated the BHT-facilitated reduction of LpA and SNGFR but not of SNPF and APR in response to L-NMMA. In group 1, urinary sodium excretion (UNaV) did not change and urinary flow rate (UV) increased slightly in period 2. L-NMMA combined with BHT, however, exerted a profound diuresis and natriuresis in group 2. These effects were further exaggerated with LOS. In a fourth group of DNX rats. LOS given alone before period 2 did not affect SNGFR, SNPF, LpA, APR, UV, or UNaV. We conclude that after subacute renal denervation alpha 2-adrenergic activation sensitizes (a) LpA to reduction by NOS inhibition through an AII-dependent mechanism, and (b) SNPF and proximal tubular reabsorption to reduction by L-NMMA regardless of the AII activity. Furthermore, our results suggest a potential role for the alpha 2-adrenergic system and AII in the diuretic and natriuretic effect of systemic NOS inhibition.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, San Diego, California 92161, USA.
authors.forename: V
authors.initials: V
authors.lastname: Vallon
authors.forename: O W
authors.initials: OW
authors.lastname: Peterson
authors.forename: F B
authors.initials: FB
authors.lastname: Gabbai
authors.forename: R C
authors.initials: RC
authors.lastname: Blantz
authors.forename: S C
authors.initials: SC
authors.lastname: Thomson
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000502:physiology*; D019808:Losartan; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D001713:Biphenyl Compounds; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D013777:Tetrazoles; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan