Smoking accelerates the progression of hypertension-induced myocardial hypertrophy to heart failure in spontaneously hypertensive rats.
OBJECTIVE
Myocardial hypertrophy often develops in response to hypertension, and it is causal to and an independent predictor of heart failure. Several risk factors modify the progression of hypertrophy, the associated progressive impairment of myocardial function, and eventually the transition to overt congestive heart failure. The aim of the present study was to investigate the effects of smoking on the progression of pressure-dependent myocardial hypertrophy.


METHODS
Spontaneously hypertensive rats (SHR) were used as a model for pressure-dependent hypertrophy. SHR were exposed to mainstream smoke from the Kentucky reference cigarette 2R4F (450 microg total particulate matter/l) or to fresh air (control), 5 days a week, twice for 1 h per day with a 30-minute fresh air exposure break for 30, 60, or 90 days. Endpoints for hypertrophy-associated changes were heart weight to body weight ratio, ventricular expression of hypertrophy-associated genes, ischemic tolerance, and inotropic responsiveness to isoprenaline in post-ischemic hearts.


RESULTS
Smoke-exposed SHR showed a significant elevation in heart weight to body weight ratio, increased mRNA expression of atrial natriuretic factor (ANF), transforming growth factor (TGF)-beta(1), ornithine decarboxylase (ODC), and parathyroid hormone-related protein in both ventricles compared to controls. Hearts from smoke-exposed SHR showed a reduced recovery after 30 min global ischemia during the first 5 min of reperfusion and loss of inotropic stimulation after 30 min reperfusion. Smoke cessation was sufficient to reverse most of these alterations. WKY exposed to smoke did not develop similar changes.


CONCLUSIONS
Our data indicate that several aspects of myocardial hypertrophy are accelerated by smoking.
Meurrens
K
K
Philip Morris Research Laboratories bvba, Leuven, Belgium.
Ruf
S
S
Ross
G
G
Schleef
R
R
von Holt
K
K
Schlüter
K-D
KD
D000818:Animals; D006332:Cardiomegaly / Q000150:complications*; D018450:Disease Progression; D006333:Heart Failure / Q000209:etiology*; D006973:Hypertension / Q000150:complications*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012907:Smoking / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D016277:Ventricular Function, Left
D044162:Parathyroid Hormone-Related Protein; D011943:Receptors, Adrenergic, beta; D053773:Transforming Growth Factor beta1