Systemic and regional hemodynamic interactions of perindopril and nitrendipine in the spontaneously hypertensive rat.
Adult spontaneously hypertensive rats (SHR) were daily treated for 2 weeks with perindopril [an angiotensin-converting enzyme (ACE) inhibitor] and nitrendipine (a calcium antagonist) alone or in combination. Blood pressure (BP), heart rate (HR), and diuresis were assessed weekly in conscious rats, and systemic and regional hemodynamics were investigated by the microsphere technique at the end of the treatment in anesthetized rats. Both perindopril (2 mg.kg-1.d-1) and nitrendipine (10 mg.kg-1.d-1) decreased BP to the same extent, but perindopril exerted a longer action. The hemodynamic profile of each drug was respectively consistent with the classic ones of ACE inhibitors and calcium antagonists already described in the literature. With combination of the two treatments, effects were at least additive, except that the nitrendipine-induced tachycardia was partially reduced by perindopril. BP reduction was additive, and significant potentiation was shown at the systemic [cardiac index (CI) increase, total peripheral resistance (TPR) decrease] and some regional (hepatic, muscular, and cutaneous vasodilations) levels. These results, which are in agreement with the different mechanisms of action of the two drugs, emphasize the advantage of combining perindopril with nitrendipine for treatment of hypertension.
Institut de Recherches Internationales Servier, Neuilly-sur-Seine, France.
E
E
Scalbert
G
G
Narcisse
D
D
Abdon
J L
JL
Fauchère
J P
JP
Santoni
D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects*; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009568:Nitrendipine / Q000493:pharmacokinetics / Q000494:pharmacology*; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D007211:Indoles; D009568:Nitrendipine; D020913:Perindopril