Diminished cardiac contractile response to tetrahydropapaveroline in hypertension: role of beta-adrenoceptors and intracellular Ca(2+).

Abstract

Tetrahydropapaveroline (THP), a condensation product of ethanol-derived acetaldehyde, potentiates cardiac function through a beta-adrenergic mechanism. It is well established that beta-adrenergic activity is markedly depressed in hypertension. However, little is known about the myocardial action of THP in hypertension. In this study, the effect of THP was examined using left ventricular papillary muscles and ventricular myocytes from 10-week-old normotensive (WKY) and spontaneously hypertensive (SHR) rats. The mechanical parameters evaluated include: peak tension developed (PTD), peak twitch amplitude (PTA), time-to-PTD/PTA (TPT/TPS), time-to-90% relaxation/relengthening (RT(90)/TR(90)), and the maximal velocities of contraction/shortening and relaxation/relengthening (+/-VT/+/-dL/dt). Intracellular Ca(2+) transients were measured as fura-2 fluorescence intensity changes (delta FFI). THP (0.01-100 microM) produced a concentration-dependent increase in myocardial contraction on muscles and myocytes from both groups of animals. However, preparations from the SHR group were generally less responsive to THP than their normotensive counterparts. The increase in contractility by THP was associated with increases in delta FFI and +/-VT, and shortening of TPT/TPS and RT(90)/TR(90). The role of beta-adrenoceptor(s) in the mechanism of action of THP was explored using specific beta-receptor subtype antagonists CGP 207.12A (beta(1)) and ICI 118,551 (beta(2)). In preparations from both WKY and SHR hearts, the THP-induced increase in cardiac contractility was either attenuated or blocked by CGP 207. 12A and ICI 118,551. These results indicate that THP exhibits a positive action on myocardial contraction that is mediated, in part, through both beta(1) and beta(2) adrenergic receptors. This cardiac inotropic response, however, is markedly diminished in hypertension, which is due possibly to alterations in beta-adrenergic signal transduction.

• Authors: J Ren, B W Smude, M L Pavlik, R A Brown
• Journal: Alcohol (Fayetteville, N.Y.) (Alcohol) Vol. 21 Issue 2 Pg. 149-59 (Jun 2000) ISSN: 0741-8329 [Print] United States
• PMID: 10963938 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenergic beta-Antagonists
• Receptors, Adrenergic, beta
• Tetrahydropapaveroline
• Calcium

Topics

• Adrenergic beta-Antagonists (pharmacology)
• Animals
• Biomechanical Phenomena
• Calcium (metabolism)
• Heart Ventricles (pathology)
• Hypertension (pathology, physiopathology)
• Male
• Muscle Contraction (drug effects)
• Myocardial Contraction (drug effects)
• Papillary Muscles (physiopathology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptors, Adrenergic, beta (physiology)
• Stimulation, Chemical
• Tetrahydropapaveroline (pharmacology)