Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension.
OBJECTIVE
Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication.


METHODS
Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: > or = 4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-L-arginine (L-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h).


RESULTS
L-NMMA dose-dependently increased mean arterial pressure with 5 +/- 2 mmHg and systemic vascular resistance with 24 +/- 5% at maximum dose, whereas cardiac output decreased (all P < 0.001). Enalapril and nifedipine treatment decreased blood pressure, while the L-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45 +/- 7% and nifedipine: 46 +/- 8%; both P < 0.01). L-NMMA also dose-dependently decreased renal blood flow by 58 +/- 8% at maximum dose (P < 0.001), but neither drug potentiated these effects.


CONCLUSIONS
These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney.
Dijkhorst-Oei
L T
LT
Department of Nephrology and Hypertension, University Hospital, Utrecht, The Netherlands.
Beutler
J J
JJ
Stroes
E S
ES
Koomans
H A
HA
Rabelink
T J
TJ
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004656:Enalapril; D019001:Nitric Oxide Synthase; D009543:Nifedipine