Dissociation of chronotropic and inotropic responses in the rat heart during sympathetic stimulation

It is not fully resolved how the chronotropic and inotropic responses alter depending on the strength or duration of stimulation, and how the alpha-vasoconstrictor effect competes with metabolic vasodilation during sympathetic stimulation. The present study investigated the effects of differential frequency stimuli on these responses in rat hearts during sympathetic stimulation while keeping the left ventricular end-diastolic volume constant. The heart was perfused at a constant flow or pressure with a modified Krebs-Henseleit solution. Electrical stimulation of sympathetic nerves (SNS) was performed at 4 frequencies (0.2, 0.5, 1 and 3 Hz) for 90 s in pithed rats without or with an alpha(1) or alpha(2) adrenergic receptor antagonist. The heart rate progressively increased during 3-Hz SNS (33+/-10% at 30 s, 38+/-14% at 90 s), whereas the inotropic action peaked at about 30 s and then decreased (left ventricular systolic pressure +23+/-8% at 30 s, -1+/-13% at 90 s). This phenomenon indicates a negative staircase, in spite of a gradual increase in norepinephrine release. The reduction of contractility did not differ from that shown by constant atrial pacing with an equivalent rate. The coronary alpha(1)-vasoconstrictor response was competitive with metabolic vasodilation only in the early phase of stimulation and the alpha(2)-vasoconstrictor action had little contribution to the regulation of coronary circulation. The fact that these results differ from previous findings suggests that sympathetic regulation of the heart should be reconsidered, although direct application of the present results to humans is not clear because of species differences.