Effects of spiraprilic acid, an angiotensin converting enzyme inhibitor, on large artery compliance in anesthetized dogs. 1987

R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
Department of Pharmacology, Schering Corporation, Bloomfield, New Jersey 07003.

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.

UI MeSH Term Description Entries
D008297 Male Males
D010654 Phenylbutyrates Derivatives of 4-phenylbutyric acid, including its salts and esters.
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D003187 Compliance Distensibility measure of a chamber such as the lungs (LUNG COMPLIANCE) or bladder. Compliance is expressed as a change in volume per unit change in pressure.
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004656 Enalapril An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE. Enalapril Maleate,MK-421,MK421,Renitec,Renitek,MK 421,Maleate, Enalapril
D005260 Female Females
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006852 Hydrochlorothiazide A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Dichlothiazide,Dihydrochlorothiazide,Esidrex,Esidrix,HCTZ,HydroDIURIL,Hypothiazide,Oretic,Sectrazide

Related Publications

R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
February 1980, Japanese journal of pharmacology,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
January 1986, Journal of cardiovascular pharmacology,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
February 1989, Journal of cardiovascular pharmacology,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
April 1992, Arzneimittel-Forschung,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
October 1993, Journal of cardiovascular pharmacology,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
January 1985, Journal of cardiovascular pharmacology,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
September 1977, European journal of pharmacology,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
September 1979, Research communications in chemical pathology and pharmacology,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
November 1989, Bulletin of the Osaka Medical College,
R W Watkins, and E J Sybertz, and A Antonellis, and K Pula
March 1986, Japanese journal of pharmacology,
Copied contents to your clipboard!