Protein kinase C regulates unloading contraction of cardiomyocytes in hypertrophic heart of spontaneously hypertensive rat / 生理学报

ABSTRACT

The activation of protein kinase C (PKC) is not only a pivotal node during cardiac hypertrophy in chronic pressure-overloaded heart, but also involved in the regulation of cardiac contractility. The aim of this paper was to observe PKC modulation in cardiac contractility at different stages of cardiac hypertrophy in spontaneously hypertensive rat (SHR). The cardiomyocytes were isolated from 4- and 10-month-old normotensive Wistar-Kyoto (WKY) and SHR rat hearts. The shortening amplitude of unloading contraction in cardiomyocytes was observed by an Edge Detector system. The shortening amplitude in WKY rat cardiomyocytes increased gradually as the stimulating frequency increased from 1 to 3 Hz. The shortening amplitude was positively correlated with stimulating frequency. The shortening amplitude in 4-month-old SHR group was enhanced as compared with that in WKY group at the same stimulating frequency. When the stimulating frequency increased, the shortening amplitude did not increase in 4-month-old SHR group. There was no difference in shortening amplitude between 10-month-old SHR and WKY groups at 1-Hz stimulating frequency. But the shortening amplitude in 10-month-old SHR group decreased when the stimulating frequency increased to 3 Hz. The perfusion of 50, 100 or 200 nmol/L PMA (a non-specific agonist of PKCs) significantly reduced the shortening amplitude in WKY and SHR groups. The shortening amplitude was reduced to (69.8±1.9)%, (58.2±2.2)% and (22.7±2.5)% (all P<0.01), respectively, in WKY group, as compared with that in HEPES buffer perfusion (100%). It was reduced to (6.1±0.7)%, (2.4±0.2)% and (12.5±2.6)% (all P<0.01) in 4-month-old SHR group, and (65.7±1.6)%, (53.9±4.0)% and (16.3±2.0)% (all P<0.01) in 10-month-old SHR group. The decreases in shortening amplitude in 4-month-old SHR group were more significant than those in 10-month-old SHR and WKY groups. On the other hand, 200 nmol/L of staurosporine, an inhibitor of PKC, significantly increased the shortening amplitude of cardiomyocytes in WKY, 4-month-old SHR, and 10-month-old SHR groups by (63.63±4.53)%, (80.82±4.61)% and (80.97±4.59)%, respectively (all P<0.05). The results suggest that the PKC isoforms inducing negative inotropic effect may be activated at the early stage of cardiac hypertrophy in SHR rats, and are possibly involved in the modulation of cardiac contractility. The activated PKC isoforms return to their normal activity at the stable stage of cardiac hypertrophy in SHR rats.