The effect of nitric oxide inhibition on the renin response to frusemide, in man

• Published in: British journal of clinical pharmacology Vol. 48; no. 3; pp. 355 - 360
• Main Authors: Lee, Alison F. C., Kiely, David G., Coutie, Wendy J., Struthers, Allan D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.1999; Blackwell Science; Blackwell Science Inc
• Subjects: Adult; Biological and medical sciences; blood pressure; Blood Pressure - drug effects; Cross-Over Studies; Diuretics - pharmacology; Double-Blind Method; Drug Interactions; Endocrine kidney. Renin-angiotensin-aldosterone system; Enzyme Inhibitors - pharmacology; frusemide; Fundamental and applied biological sciences. Psychology; Furosemide - pharmacology; Heart Rate - drug effects; Humans; Male; nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - physiology; omega-N-Methylarginine - pharmacology; Original; phenylephrine; renin; Renin - metabolism; Vertebrates: endocrinology; Human; Sulfanilamide derivatives; Sulfonamide; Intravenous administration; Healthy subject; Enzyme; Furosemide; Diuretic; Peptidases; Renin; Nitric oxide; Phenylephrine; Hydrolases; Antihypertensive agent; Aspartic endopeptidases; Hemodynamics; Inhibition; Mechanism of action; Comparative study
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.1999.00014.x

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 μg 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−1P<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−1P<0.01). Phenylephrine 0.5 μg 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−1P<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.