title: Angiotensin-converting enzyme inhibition improves cardiac function. Role of bradykinin.
abstract: The effect of chronic low- and high-dose treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril (0.01 and 1 mg/kg per day) on the development of hypertension and left ventricular hypertrophy as well as on functional and biochemical alterations of the heart was studied in stroke-prone spontaneously hypertensive rats treated prenatally and subsequently up to the age of 20 weeks. The contribution of endogenous bradykinin potentiation to the ACE inhibitor actions was assessed by cotreatment of rats with the bradykinin B2-receptor antagonist Hoe 140 (500 micrograms/kg per day SC) from 6 to 20 weeks of age. High- but not low-dose ACE inhibitor treatment prevented the development of hypertension and left ventricular hypertrophy. Chronic bradykinin receptor blockade did not attenuate the antihypertensive and antihypertrophic actions of ramipril. High-dose ramipril treatment improved cardiac function, as demonstrated by an increase in left ventricular pressure (29.9%), dP/dtmax (34.9%), and coronary flow (22.1%), without a change in heart rate. The activities of lactate dehydrogenase and creatine kinase and lactate concentration in the coronary effluent were reduced by 39.3%, 55.5%, and 66.7%, respectively. Myocardial tissue concentrations of glycogen and the energy-rich phosphates ATP and creatine phosphate were increased by 31.3%, 39.9%, and 73.7%, respectively, whereas lactate was decreased by 20.8%. Chronic low-dose ACE inhibitor treatment led to a pattern of changes in cardiodynamics and cardiac metabolism similar to that observed with the high dose. All ACE inhibitor-induced effects on cardiac function and metabolism were abolished by chronic bradykinin receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Christian Albrechts University of Kiel, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Gohlke
authors.forename: W
authors.initials: W
authors.lastname: Linz
authors.forename: B A
authors.initials: BA
authors.lastname: Schölkens
authors.forename: I
authors.initials: I
authors.lastname: Kuwer
authors.forename: S
authors.initials: S
authors.lastname: Bartenbach
authors.forename: A
authors.initials: A
authors.lastname: Schnell
authors.forename: T
authors.initials: T
authors.lastname: Unger
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D002561:Cerebrovascular Disorders / Q000209:etiology; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011247:Pregnancy; D017257:Ramipril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D007773:Lactates; D010725:Phosphocreatine; C065679:icatibant; D000255:Adenosine Triphosphate; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D017257:Ramipril; D001920:Bradykinin