BIOMAT Database Logo BIOMAT Database Logo

Angiotensin II subtype-1 receptor blockade during the development of left ventricular hypertrophy in dogs: effects on ventricular and myocyte function. 1997

F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, U.S.A.

Inhibition of the angiotensin-converting enzyme (ACE) in developing left ventricular (LV) hypertrophy has been demonstrated to have inhibitory effects on myocardial growth. An important mechanism of action of ACE inhibition is modulation of myocardial AT1 Ang II-receptor activity. However, whether and to what extent AT1 Ang II-receptor blockade may influence LV and myocyte function during the hypertrophic process remains unclear. Accordingly, our project examined the relation between changes in LV and myocyte function during the LV hypertrophic process that occurs after recovery from long-term rapid pacing. Dogs were randomly assigned to the following treatment groups: (a) Pace and Recovery, long-term rapid pacing (4 weeks; 216 +/- 2 beats/min) followed by a 4-week recovery period (n = 6); (b) Recovery/AT1 Block, concomitant AT1 Ang II-receptor blockade [irbesartan (SR 47436; BMS-186295) 30 mg/kg b.i.d.] administered during the 4-week recovery period (n = 5); and (c) Control, sham controls (n = 6). There was no difference in mean arterial pressure in any of the three groups. With pacing and recovery, LV end-diastolic volume and mass were increased by >50% from control values. The significant LV remodeling that occurred with recovery from long-term rapid pacing was associated with a decline in LV ejection fraction (59 +/- 3% vs. 68 +/- 4%) and myocyte velocity of shortening (43 +/- 3 microm/s vs. 63 +/- 3 microm/s) when compared with controls (p < 0.05). With recovery from long-term rapid pacing, LV myocyte length (176 +/- 6 microm vs. 150 +/- 1 microm) and cross-sectional area were increased (292 +/- 7 microm2 vs. 227 +/- 6 microm2) compared with controls (p < 0.05). With AT1 Ang II block during recovery from rapid pacing, LV end-diastolic volume was similar to untreated recovery values, but LV mass was normalized. LV ejection fraction was not different from control values with AT1 Ang II-receptor block. Steady-state myocyte velocity of shortening with AT1 Ang II block was similar to control values (55 +/- 5 microm/s), but percentage shortening remained reduced from control (3.55 +/- 0.37% vs. 4.71 +/- 0.12%, respectively, p < 0.05) and was similar to untreated recovery (3.59 +/- 0.23%). With AT1 Ang II block, myocyte length was similar to untreated recovery values, but cross-sectional area was reduced (260 +/- 5 microm2, p < 0.05). Thus AT1 Ang II-receptor blockade instituted in this model of developing LV hypertrophy, significantly reduced LV mass but did not reduce the degree of LV dilation. The cellular basis for these effects of AT1 Ang II-receptor blockade included persistent abnormalities in LV myocyte geometry. AT1 Ang II-receptor blockade improved certain indices of myocyte contractile function from untreated hypertrophy values. These findings suggest that in this pacing-recovery model, the development of LV hypertrophy and myocyte contractile dysfunction may be caused, at least in part, by AT1 Ang II-receptor activation.

UI MeSH Term Description Entries
D008297 Male Males
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
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
D005260 Female Females
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000077405 Irbesartan A spiro compound, biphenyl and tetrazole derivative that acts as an angiotensin II type 1 receptor antagonist. It is used in the management of HYPERTENSION, and in the treatment of kidney disease. 2-N-Butyl-3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1,3-diazaspiro(4,4)non-1-en-4-one,Aprovel,Avapro,BMS 186295,BMS-186295,Karvea,SR 47436,SR-47436,SR47436
D000806 Angiotensin-Converting Enzyme Inhibitors A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. ACE Inhibitor,ACE Inhibitors,Angiotensin Converting Enzyme Inhibitor,Angiotensin I-Converting Enzyme Inhibitor,Angiotensin-Converting Enzyme Inhibitor,Kininase II Inhibitor,Kininase II Inhibitors,Angiotensin I-Converting Enzyme Inhibitors,Angiotensin-Converting Enzyme Antagonists,Antagonists, Angiotensin-Converting Enzyme,Antagonists, Kininase II,Inhibitors, ACE,Inhibitors, Angiotensin-Converting Enzyme,Inhibitors, Kininase II,Kininase II Antagonists,Angiotensin Converting Enzyme Antagonists,Angiotensin Converting Enzyme Inhibitors,Angiotensin I Converting Enzyme Inhibitor,Angiotensin I Converting Enzyme Inhibitors,Antagonists, Angiotensin Converting Enzyme,Enzyme Antagonists, Angiotensin-Converting,Enzyme Inhibitor, Angiotensin-Converting,Enzyme Inhibitors, Angiotensin-Converting,II Inhibitor, Kininase,Inhibitor, ACE,Inhibitor, Angiotensin-Converting Enzyme,Inhibitor, Kininase II,Inhibitors, Angiotensin Converting Enzyme

Related Publications

F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Differential effects of angiotensin II receptor blockade on pressure-induced left ventricular hypertrophy and fibrosis in rats.
February 1999, Journal of molecular and cellular cardiology,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Diastolic properties in canine hypertensive left ventricular hypertrophy: effects of angiotensin converting enzyme inhibition and angiotensin II type-1 receptor blockade.
January 1997, Cardiovascular research,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Blockade of angiotensin II type 1 receptor improves the arrhythmia morbidity in mice with left ventricular hypertrophy.
March 2006, Circulation journal : official journal of the Japanese Circulation Society,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Concomitant endothelin receptor subtype-A blockade during the progression of pacing-induced congestive heart failure in rabbits. Beneficial effects on left ventricular and myocyte function.
April 1997, Circulation,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Effects of angiotensin II receptor blockade on hypoxia-induced right ventricular hypertrophy in rats.
November 1997, Journal of molecular and cellular cardiology,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Early and late haemodynamic and morphological effects of angiotensin II subtype 1 receptor blockade during genetic hypertension development.
June 1995, Journal of hypertension,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Relative effects of alpha 1-adrenoceptor blockade, converting enzyme inhibitor therapy, and angiotensin II subtype 1 receptor blockade on ventricular remodeling in the dog.
December 1994, Circulation,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Left ventricular hypertrophy and angiotensin II receptor blocking agents.
January 2005, Current medicinal chemistry. Cardiovascular and hematological agents,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Effects of angiotensin II receptor blockade-based therapy with losartan on left ventricular hypertrophy and geometry in previously treated hypertensive patients.
January 2006, Blood pressure,
F G Spinale, and H H Holzgrefe, and J D Walker, and R Mukherjee, and S B Kribbs, and J R Powell, and M Antonaccio
Left ventricular hypertrophy and renin-angiotensin system blockade.
June 2009, Current hypertension reports,
Copied contents to your clipboard!