Structural and functional consequences of minoxidil-induced cardiac hypertrophy.
Minoxidil, a potent arteriolar vasodilator, is used clinically as an antihypertensive agent, providing blood pressure control in patients who are resistant to conventional drug therapy. In spite of its antihypertensive effects, however, minoxidil treatment does not result in regression of cardiac hypertrophy. Laboratory studies have shown that minoxidil treatment actually causes cardiac enlargement when administered to normotensive animals. The mechanism of minoxidil-induced cardiac hypertrophy and its consequences for the myocardium have not been determined. Because cardiac hypertrophy is a significant independent risk factor for cardiovascular morbidity and mortality, it is important to understand this dissociation between blood pressure and cardiac enlargement and also to consider the possible impact of such findings on the clinical use of minoxidil. In the investigation presented here, we examined the structure and function of cardiac muscle from normotensive rats who developed myocardial hypertrophy after minoxidil treatment. Data demonstrate that minoxidil produces enlargement of the left ventricle, right ventricle and interventricular septum. The right ventricular enlargement produced by minoxidil treatment is due to an increase in myocyte cross-sectional area, a finding which may suggest pressure overload of the right ventricle. Left ventricular and septal enlargement in this model cannot be totally accounted for by an increase in myocyte cross-sectional area, suggesting that minoxidil causes enlargement by a mechanism other than pressure overload in these areas of the heart. Functionally, left ventricular papillary muscles from hearts with minoxidil-induced hypertrophy develop force which is equal to that developed by control muscles, but contract and relax more slowly than muscles from control hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Moravec
C S
CS
Department of Cardiovascular Biology, Cleveland Clinic Foundation, Ohio.
Ruhe
T
T
Cifani
J R
JR
Milovanovic
M
M
Khairallah
P A
PA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced* / Q000503:physiopathology*; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D008914:Minoxidil / Q000633:toxicity*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D010210:Papillary Muscles / Q000033:anatomy & histology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D008914:Minoxidil