Changes in renal and systemic hemodynamics after NO-synthase inhibition in males with family history of hypertension.
BACKGROUND
Nitric oxide (NO) plays an important role in the regulation of blood pressure and renal hemodynamics.


METHODS
To further investigate the role of NO in human hypertension, we studied the effect of systemic injection of N(G)-monomethyl-L-arginine (L-NMMA) on renal hemodynamics, urinary sodium excretion (FE(Na)), systemic hemodynamics and several vasoactive hormones in 5 healthy male subjects with (group H) and without (group N) family history of hypertension. An intravenous infusion of L-NMMA (3 mg/kg over 10 min) or placebo was given in a randomized, double-blinded manner. GFR and ERPF were measured by inulin- and PAH-clearances. Norepinephrine infusion (0.1 microg/kg/min over 60 min) served as vasoconstrictive control infusion.


RESULTS
L-NMMA induced a significant decrease in ERPF (-135 +/- 49 vs. 7 +/- 31 ml/min/1.73 m(2) with placebo, p < 0.05), a decrease in FE(Na) (-1.2 +/- 0.6% with L-NMMA vs. 0.0 +/- 0.1% with placebo), and a significant increase in diastolic blood pressure (+7 +/- 1 vs. -2 +/- 1 mm Hg with placebo) in group N, only. A sustained drop in plasma renin activity (-0.1 +/- 0.1 vs. 0.3 +/- 0.1 ng/ml/h with placebo) could also be seen in this group, only. Subjects with family history of hypertension showed minor or even no response (changes in diastolic blood pressure: L-NMMA: 5 +/- 3 mm Hg, placebo: 0 +/- 2 mm Hg; changes in ERPF: L-NMMA: -89 +/- 57 ml/min/1.73 m(2), placebo: -34 +/- 28 ml/min/1.73 m(2); changes in plasma renin activity: L-NMMA: -0.0 +/- 0.3 ng/ml/h, placebo: -0.1 +/- 0.2 ng/ml/h). The vasoconstrictive effect of norepinephrine infusion did not differ between both groups.


CONCLUSIONS
Our data indicate that systemic NO synthetase inhibition by L-NMMA results in a blunted effect on systemic blood pressure and the renal hemodynamic system in subjects with family history of hypertension.
Berger
Elke D
ED
University of Tübingen, Department of Internal Medicine III, Eberhard Karls University, Tübingen, Germany.
Bader
Birgit D
BD
Rüb
Norman
N
Rauscher
Matthias A S
MA
Rebenschütz
Ingo
I
Gaber
Oliver C
OC
Enderle
Markus D
MD
Risler
Teut
T
Erley
Christiane M
CM
D000328:Adult; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007275:Injections, Intravenous; D008297:Male; D008499:Medical Records; D009318:Natriuresis / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D012083:Renin