Abstract
The purpose of our study was to investigate the inotropic response to the endogenous agonist norepinephrine mediated throughalpha-1 adrenoceptors and to compare this response to that mediated through beta-adrenoceptors in failing human ventricular myocardium. We studied ex vivo the inotropic effect of norepinephrine in isometrically contracting trabecular myocardium from both ventricles of explanted hearts. By studying influence of appropriate adrenoceptor blockers, qualitative characteristics of the inotropic response and sensitivity of the inotropic response to cholinergic stimulation, it was revealed that norepinephrine evoked both alpha-1 andbeta adrenoceptor-mediated inotropic effects in failing human ventricle myocardium. Quantitatively the inotropic responses to norepinephrine varied markedly between preparations, but the mean responses elicited through the respective adrenoceptor systems were of comparable magnitude. Concomitant stimulation of alpha-1 and beta adrenoceptors by norepinephrine alone revealed a contribution of an alpha-1 adrenoceptor-mediated component to the final and unopposed inotropic response. Differential sensitivity of the two adrenoceptor systems to norepinephrine depending on etiology of heart failure and possibly also thyroid status was observed. It is concluded that norepinephrine evokes analpha-1 adrenoceptor-mediated inotropic effect comparable to that evoked through the beta adrenoceptors in failing human ventricular myocardium, and that thisalpha-1 adrenoceptor-mediated inotropic effect may be of functional importance.
Footnotes
-
Send reprint requests to: Dr. Tor Skomedal, University of Oslo, Department of Pharmacology, P.O. Box 1057 Blindern, N-0316 Oslo, Norway.
-
↵1 This work was supported by The Norwegian Research Council, The Norwegian Council on Cardiovascular Diseases, J.L. Tiedemanns Tobaksfabrik/J.H. Andresens Medisinske Fond and Anders Jahres Fond .
- Abbreviations:
- Tmax
- maximal developed tension
- TPT
- time to peak tension
- TR20
- time to relaxation to 20% level
- RT
- relaxation time
- pD2
- -log EC50
- EC50
- concentration giving half maximal effect
- TSH
- thyroid stimulating hormone
- Received July 8, 1996.
- Accepted October 29, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|