Effects of nitrendipine and cilazapril alone or in combination on hemodynamics and regional blood flows in conscious spontaneously hypertensive rats.
Nitrendipine and cilazapril are two new antihypertensive drugs with different mechanisms of action. Nitrendipine is a calcium antagonist of the dihydropyridine class which decreases directly the smooth muscle tone. Cilazapril is a new long-lasting inhibitor of angiotensin-converting enzyme which suppresses the peripheral vasoconstrictor effect of angiotensin I by inhibiting its transformation in angiotensin II. The goal of the present study was to assess the effects on hemodynamics and regional blood flows (measured with radioactive microspheres) of cilazapril and nitrendipine given alone or in combination. Cilazapril (3 mg/kg) and nitrendipine (0.3 mg/kg) were given intravenously to conscious spontaneously hypertensive rats first alone, then in combination. Both cilazapril and nitrendipine decreased mean arterial pressure to the same extent. Cilazapril increased regional blood flow only in the kidney without changing total cardiac output. In contrast, nitrendipine increased regional blood flow in nearly every organ and markedly enhanced total cardiac output. Cilazapril redistributed the cardiac output distribution toward the kidney, and nitrendipine did not change the cardiac output distribution. The combination of both nitrendipine and cilazapril produced a stronger antihypertensive effect than each drug alone. The peripheral vasodilatation with the combination was not as marked as with nitrendipine alone but was associated with the same redistribution of the cardiac output toward the kidney as with cilazapril. We conclude that after acute intravenous administration the combination of cilazapril and nitrendipine produced hemodynamic effects which cannot be induced by each drug used alone. Such a therapeutic profile may be useful in patients with high blood pressure or heart failure.
Clozel
J P
JP
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co., Ltd., Basel, Switzerland.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D017315:Cilazapril; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D009568:Nitrendipine