The effect of nitric oxide inhibition on the renin response to frusemide, in man.
OBJECTIVE
We wished to see if renin release in man was inhibited by nitric oxide blockade, suggesting a role for nitric oxide in renin release. Evidence from animal studies has shown variable effects on renin release depending on the model and stimulus used.


METHODS
Ten normal male volunteers, received either L-NMMA as a front loaded infusion (4 mg kg-1 bolus, with 4 mg kg-1 infusion), or placebo, followed by an intravenous bolus of 5 mg frusemide to stimulate renin. To investigate whether any alteration in renin release was due to the pressor effect of the L-NMMA, the experiment was repeated using an equipressor dose of phenylephrine (0.5 microg kg-1 min-1 ).


RESULTS
L-NMMA caused the expected increase in mean arterial pressure (96+/-2.6 vs 89+/-3.3 mmHg P<0.05 [mean+/-s.e.mean]), and a reduction in heart rate (59+/-3.6 vs 67+/-2.5 beats min-1 P<0.05). L-NMMA completely blocked the renin rise following the bolus of frusemide (1.18+/-0.196 vs 1.96+/-0.333 ng ml-1 h-1 P<0.01). Phenylephrine 0.5 microg kg-1 min-1 produced very similar haemodynamic effects to L-NMMA, and also suppressed the renin response to frusemide (1.43+/-0.290 vs 2.67+/-0.342 ng ml-1 h-1 P<0. 01).


CONCLUSIONS
In man, the renin inhibition seen with NO synthesis inhibition is similar to that seen with a standard pressor stimulus, hence inhibition of renin in man by L-NMMA, may be due to both direct effects on macula densa cells and indirect haemodynamic effects.
Lee
A F
AF
Department of Medical Cardiology, Glasgow Royal Infirmary, Glasgow.
Kiely
D G
DG
Coutie
W J
WJ
Struthers
A D
AD
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004232:Diuretics / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D012083:Renin / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004232:Diuretics; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005665:Furosemide; D012083:Renin