Effects of spiraprilic acid, an angiotensin converting enzyme inhibitor, on large artery compliance in anesthetized dogs.
The present study examined the actions of spiraprilic acid, a new non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor upon aortic compliance (AC) in anesthetized dogs. Enalaprilic acid was examined for comparative purposes. AC was determined via sonomicrometric determination of the ratio of aortic systolic-diastolic diameter (mm) and arterial pulse pressure (mmHg). One AC unit (ACU) equals 10(-3) mm/mmHg. In non-thiazide pretreated animals, spiraprilic acid (1 mg/kg i.v.), caused a sustained hypotensive response of 21 +/- 3 mmHg (P less than .05). At the same time, aortic systolic and diastolic dimensions were reduced from basal values of 8.17 +/- 0.45 and 7.95 +/- 0.40 mm by 0.19 +/- 0.07 (P less than .05) and 0.29 +/- 0.10 mm (P less than .05), respectively. The aortic systolic-diastolic dimension rose significantly by 0.10 +/- 0.01 mm. Since pulse pressure was unchanged, AC rose from a basal value of 4.6 +/- 0.8 ACU by 1.7 +/- .3 ACU (P less than .05). Similar effects were observed with enalaprilic acid. In dogs pretreated orally with 5 mg/kg hydrochlorothiazide (HCTZ) twice daily for 3 days, spiraprilic and enalaprilic acids caused slightly greater falls in blood pressure (34 +/- 7 and 30 +/- 4 mmHg, respectively) than in nonpretreated dogs. However, the onset of the hypotension effect was more rapid for both ACE inhibitors in HCTZ-pretreated dogs. Effects of spiraprilic and enalaprilic acid upon aortic dimensions were similar to those observed in non-HCTZ pretreated animals. The data illustrate that the ACE inhibitors spiraprilic and enalaprilic acids not only lower blood pressure but also enhance large artery compliance.
Watkins
R W
RW
Department of Pharmacology, Schering Corporation, Bloomfield, New Jersey 07003.
Sybertz
E J
EJ
Antonellis
A
A
Pula
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D003187:Compliance; D004285:Dogs; D004347:Drug Interactions; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000494:pharmacology; D008297:Male; D010654:Phenylbutyrates / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D010654:Phenylbutyrates; D011355:Prodrugs; D013141:Spiro Compounds; D006852:Hydrochlorothiazide; D004656:Enalapril; C056109:SCH 33861; D015773:Enalaprilat