M. Vilapetroff et al., MECHANISM OF NEGATIVE LUSITROPIC EFFECT OF ALPHA(1)-ADRENOCEPTOR STIMULATION IN CAT PAPILLARY-MUSCLES, American journal of physiology. Heart and circulatory physiology, 39(2), 1996, pp. 701-709
Experiments were performed in cat papillary muscles to explore the mec
hanisms by which alpha(1)-adrenoceptor stimulation affects myocardial
relaxation. Phenylephrine (PE; 10 mu M) + atenolol (1 mu M; n = 8 expe
riments) produced a negative lusitropic effect, i.e., a prolongation o
f half-relaxation time (t(1/2); time to 50% relaxation) by 30 +/- 10%
(P < 0.05) and a proportionally smaller increase in maximal velocity o
f relaxation (-T) than in maximal velocity of contraction (+T), which
significantly increased the ratio +T/-T. A similar increase in contrac
tility, produced by increasing calcium, failed to significantly change
t(1/2) and +T/-T. PE-induced negative lusitropic effect was significa
ntly inhibited by two protein kinase C (PKC) inhibitors, staurosporine
(0.1 mu M) and chelerythrine (10 mu M). PE also increased intracellul
ar pH by 0.18 +/- 0.05 pH units (P < 0.05, n = 4), as measured by the
fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Int
racellular alkalosis and the negative lusitropic effect of PE were pre
vented by the Na+/H+ exchanger inhibitor ethylisopropylamiloride (10 m
u M). No significant changes in calcium myofilament sensitivity and ma
ximal tension were detected in trabeculae treated with PE either befor
e or after chemical skinning. These results indicate that a Na+/H+ exc
hanger-induced intracellular alkalosis, possibly mediated by PKC activ
ation, may fully account for the negative lusitropism of alpha(1)-adre
noceptor stimulation.