Enalapril in experimental hypertension and acute heart failure: comparison with calcium channel blockers.
The hemodynamic effects of enalaprilat (MK-422) and lisinopril (MK-521) were compared with the calcium channel blocker felodipine in dogs with ischemic left ventricular (LV) failure. The combination of nitrendipine plus enalapril was also examined in ischemic failure and in rats with spontaneous hypertension. In anesthetized dogs coronary embolization with 50 micron plastic microspheres reduced cardiac output and LV dP/dt max by approximately 40%, and LV end-diastolic pressure increased to greater than 13 mm Hg. Enalaprilat and lisinopril reduced mean arterial pressure by a maximum of 20 mm Hg and total peripheral resistance by approximately 30%. Left ventricular dP/dt:LVP, which was substantially decreased by embolization, was slightly increased by both angiotensin converting enzyme (ACE) inhibitors. The calcium entry blockers felodipine and nitrendipine qualitatively produced many of the same hemodynamic effects as the ACE inhibitors, but, in addition, they markedly reduced coronary resistance, increased myocardial blood flow, and did not alter cardiac contractility (LV dP/dt max). In spontaneously hypertensive rats single doses of nitrendipine (1.25 to 5.0 mg/kg per os) and enalapril (0.3 and 3.0 mg/kg per os) reduced mean arterial pressure, but differences were observed in the onset (enalapril 2 h versus nitrendipine 0.5 h), the duration of action, and magnitude of effect. In terms of blood pressure lowering, nitrendipine, 5.0 mg/kg per os, was clearly additive to 3.0 mg/kg per os of enalapril, but other combinations (enalapril, 3 mg/kg per os plus 0.625 mg/kg of nitrendipine or enalapril, 0.3 mg/kg per os plus 0.625 mg/kg nitrendipine) were not.(ABSTRACT TRUNCATED AT 250 WORDS)
Sweet
C S
CS
Ludden
C T
CT
Adkins
E
E
Seymour
A A
AA
Emmert
S
S
Ribeiro
L G
LG
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004285:Dogs; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000031:analogs & derivatives / Q000627:therapeutic use*; D015773:Enalaprilat; D015736:Felodipine; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy*; D017706:Lisinopril; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D009568:Nitrendipine; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004656:Enalapril; D009568:Nitrendipine; D017706:Lisinopril; D015773:Enalaprilat; D009543:Nifedipine; D015736:Felodipine