α1-Adrenergic stimulation increases the Vmax of isolated myocardial papillary muscles

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Abstract
α-Adrenergic agonists have been shown to increase the tension developed by myocardial muscle. However, their effects on the maximum velocity of unloaded muscle shortening (Vmax) have not been rigorously examined. In this study, the contractile effects of the α-adrenergic agonist phenylephrine were examined in the presence of propranolol in papillary muscles of two species, the dog and the rabbit. In rabbit papillary muscles studied at physiological calcium concentrations (1.25 mM), phenylephrine increased all indices of contractility (Vmax, tension, and maximum rate of tension developed (dT/dt)) starting at 10−8 M. The percent increase in Vmax (121 ± 8%) was less than that of tension (188 ± 20%, p < 0.05) and dT/dt (262 ± 35%, p < 0.01). These findings occurred at both 29 and 35 °C and were inhibited by adding 10−5 M prazosin. Increasing extracellular calcium concentration from 1.25 to 15 mM caused changes in twitch configuration that were significantly different from those of phenylephrine. Calcium increased all indices of contractility more than did phenylephrine. This was particularly true for dT/dt (502 ± 82 vs. 262 ± 35% for phenylephrine, p < 0.01). Nonetheless, the ratio of increase in tension to increase in Vmax under both experimental conditions was similar (the increase in Vmax was 64% of that of tension with phenylephrine and 69% with increased calcium). At 1.25 mM calcium, the increase in contractility caused by phenylephrine was much smaller in dog myocardium as compared with rabbit myocardium. Rather, the effects of phenylephrine on dog myocardium studied at 1.25 mM calcium resembled that of rabbit myocardium studied at 15 mM calcium. We conclude that (i) α1-adrenergic receptor stimulation increases all indices of contractility at a similar threshold concentration but increases Vmax relatively less; (ii) despite markedly different effects on the intensity of the cytosolic calcium transient and twitch configuration characteristics, the increase in Vmax relative to tension caused by phenylephrine is similar to that caused by increasing extracellular calcium concentration; (iii) species differences in myocardial contractile response to α1-adrenergic stimulation exist, and that some of these differences can be abolished by altering extracellular calcium.Key words: α1-adrenergic, Vmax, contractility, calcium.

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