Relative roles of nitric oxide, prostanoids and angiotensin II in the regulation of canine glomerular hemodynamics. A micropuncture study.
Glomerular hemodynamics are controlled by a variety of physical, nervous and hormonal factors including the potent vasoconstrictors, angiotensin (ANG) II and endothelin-1 (ET-1), and the vasodilator prostanoids (prostaglandin = PG) and nitric oxide (NO). Since no micropuncture data on the canine kidney exist with respect to the relative roles of the endogenous vasoactive hormones/autacoids NO, PG and ANG II in modulating glomerular hemodynamics, in the present study using the micropuncture technique in anesthetized dogs on a normal salt intake, we investigated the relative effects of these hormones/autacoids by means of the L-arginine analog, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME), a competitive NO synthase (NOS) inhibitor, the cyclooxygenase inhibitor indomethacin (INDO), and the AT(1) receptor blocker EXP 3174. An intrarenal arterial (i.r.a.) bolus (within 5 min) of 2.5 mg of L-NAME led to a significant decrease in total renal blood flow (RBF) and single nephron glomerular blood flow (SNGBF) from 4.46 +/- 0.51 to 3.52 +/- 0.41 ml/min/g kidney weight and from 0.393 +/- 0.041 to 0.341 +/- 0.037 microl/min (p < 0.01), respectively, without a change in glomerular filtration rate (GFR). The increase in arteriolar resistance was more pronounced at the efferent (+31%) than at the afferent (+13%) arteriole, and K(f) decreased from 4.5 +/- 0.5 to 3.7 +/- 0.4 nl/min/mm Hg (p < 0.01). INDO (5 mg/kg i.v. bolus followed by 0.17 mg/kg/min i.v.) had no effect on glomerular hemodynamics. EXP 3174 (30 microg/kg/min i.r.a.) increased RBF and SNGBF from 4.35 +/- 0.45 to 4.99 +/- 0.50 ml/min/g kidney weight and from 0.403 +/- 0.028 to 0.478 +/- 0.039 microl/min (p < 0.01), respectively, without an effect on GFR. It reduced the efferent arteriolar resistance by 25% as compared to 13% at the afferent arteriolar level. EXP 3174 increased K(f) from 5.1 +/- 0.4 to 8.1 +/- 0.6 mm Hg (p < 0.01) in the presence of a decrease in effective filtration pressure from 13.2 +/- 1.7 to 8.3 +/- 1.0 mm Hg (p < 0.01). The glomerular hemodynamic effects of L-NAME were unaltered by pretreatment with INDO or EXP 3174, whereas its tubular effects were restored in the presence of EXP 3174. Thus, from these first micropuncture data in the anesthetized dog on a normal sodium intake we conclude that (1) acute intrarenal inhibition of NOS by L-NAME decreases RBF and SNGBF due to vasoconstriction of the afferent and, more pronounced, efferent arterioles. Since L-NAME simultaneously decreases K(f), GFR remains unaltered. (2) These renal hemodynamic effects of NOS inhibition were not mediated by prostanoids or intrarenal ANG II. Thus, the tonic activity of intrarenal NOS plays an important role in maintaining glomerular hemodynamics in the canine kidney.
Renal Section, Medical Policlinic, University of Bonn, Bonn, Germany. hkramer@uni-bonn.de
Herbert J
HJ
Kramer
Vladislav
V
Horacek
Angela
A
Bäcker
Ivana
I
Vaneckova
Jiri
J
Heller
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply*; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011453:Prostaglandins; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C066026:losartan carboxylic acid; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin