Key result
l-NMMA completely blocked the renin rise following a bolus of frusemide compared to placebo (1.18 vs 1.96 ng ml-1 h-1, p<0.01), an effect similarly seen with the pressor phenylephrine.
Why the study?
Does nitric oxide synthesis inhibition with L-NMMA reduce frusemide-stimulated renin release in healthy male volunteers?
RCT (n=10)
Double-blind
Randomized
No
Does nitric oxide synthesis inhibition with L-NMMA reduce frusemide-stimulated renin release in healthy male volunteers?
Inhibition of nitric oxide synthesis with L-NMMA suppresses frusemide-stimulated renin release in humans, an effect that appears to be largely driven by indirect hemodynamic changes.
Answers are grounded in this paper and cite their sources.
Alerts to potential renin suppression with NO inhibitors during diuretic use; extends animal data on hemodynamic mediation to healthy humans.
AIMS: 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.
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Lee et al. (1999) conducted an RCT in Healthy volunteers (n=10). l-NMMA vs. Placebo was evaluated on Renin response to frusemide (ng ml-1 h-1) (p=<0.01). l-NMMA completely blocked the renin rise following a bolus of frusemide compared to placebo (1.18 vs 1.96 ng ml-1 h-1, p<0.01), an effect similarly seen with the pressor phenylephrine.
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