I. Kouchi et al., Increase in G(i alpha) protein accompanies progression of post-infarction remodeling in hypertensive cardiomyopathy, HYPERTENSIO, 36(1), 2000, pp. 42-47
Citations number
31
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Hypertensive cardiac hypertrophy and myocardial infarction (MI) are clinica
lly relevant risk factors for heart failure. There is no specific informati
on addressing signaling alterations in the sequence of hypertrophy and post
-MI remodeling. To investigate alterations in beta-adrenergic receptor G-pr
otein signaling in ventricular remodeling with pre-existing hypertrophy, MI
was induced by coronary artery ligation in Wistar-Kyoto rats (WKY) and spo
ntaneously hypertensive rats (SHR). Ten weeks after the induction of MI, th
e progression of left ventricular dysfunction and increases in plasma atria
l natriuretic peptide (ANP) and cardiac ANP mRNA were more pronounced in SH
R than WKY. In addition, the impaired contractile response to beta-adrenerg
ic stimulation was observed in the noninfarcted papillary muscle isolated f
rom SHR. Immunochemical G(s alpha) protein and beta-adrenoceptor density we
re not significantly altered by MI in both strains. However, immunochemical
G(i alpha) was increased (1.5-fold) in the noninfarcted left ventricle of
the SHR in which infarction had been induced when compared with that in SHR
that underwent sham operation. This increase was observed especially in ra
ts with a high plasma ANP level. Furthermore, there was a positive correlat
ion between G(i alpha) and the extent of post-MI remodeling in WKY. A simil
ar correlation between G(i alpha) and the extent of hypertensive hypertroph
y was observed in SHR. In conclusion, the vulnerability of hypertrophied he
arts to ischemic damage is greater than that of normotensive hearts. An inc
rease in G(i alpha) could be one mechanism involved in the transition from
cardiac hypertrophy to cardiac failure when chronic pressure overload and l
oss of contractile mass from ischemic heart disease coexist.