Loss of cardiac contractile response to tetrahydropapaveroline with advanced age and hypertension.

Tetrahydropapaveroline (THP), a condensation product of ethanol-derived acetaldehyde, potentiates cardiac function through beta-adrenoceptor. We have recently shown that THP-induced cardiac contractile action is likely due to its action at the single myocyte level, and is markedly diminished during early hypertension. Cardiac function alters with advanced age reminiscent of hypertension. This study was to examine cardiac contractile response to THP with advanced age and hypertension. Left ventricular papillary muscles and myocytes were isolated from normotensive (WKY) or hypertensive (SHR) rats, and stimulated to contract at 0.5 Hz. Mechanical parameters evaluated include: peak tension developed (PTD)/peak shortening (PS), time-to-PTD/PS (TPT/TPS), time-to-90% relaxation/relengthening (RT90/TR90), and maximal velocities of contraction/relaxation (+/- VT/+/- dLdt). Intracellular Ca2+ transients were measured as fura-2 fluorescence intensity changes (AFFI). THP (0.1-100 microM) increased PTD in 10- but not 36-wk-old WKY rat myocardium. THP elicited positive, negative or no response on PS in myocytes from 10-wk WKY, 36-wk WKY, and 36-wk SHR groups, respectively. Interestingly, THP elicited discrepant response on intracellular Ca2+ transient compared with that of myocyte shortening. THP increased AFFI in 10-wk WKY and 36-wk SHR myocytes while exhibiting a significant inhibiting action in 36-wk WKY myocytes. Lastly, THP shortened TPT/TPS, RT90/TR90 and increased +VT in all animal groups. These results indicate that the THP-induced myocardial contractile response is altered in advanced age and hypertension, in a manner similar to early stage of hypertension. It is possible that altered intracellular Ca2+ responsiveness may be involved in THP-induced action.