Contractile Response to Sympathetic Innervation in Neonatal Ventricular Cardiomyocytes of the Spontaneously Hypertensive Rat

Abstract

ABSTRACT: Differences in cardiac development between spontaneously hypertensive rats (SHR) and their normo-tensive Wistar Kyoto (WKY) controls are observed before the onset of hypertension. To determine whether intrinsic differences in myocardium or autonomic neurons might be responsible for these observations, we studied primary cultures of isolated, never previously innervated ventricular cardiomyocytes from neonatal rats of both strains, and sympathetic innervation was produced by addition of neu-rons from thoracolumbar sympathetic ganglia. Both samestrain and cross-strain innervation were compared. Amplitude and frequency of contraction were measured from video images of spontaneously contracting cells by on-line video motion analysis. Sympathetic innervation improved contractile function by 61% in SHR cardiomyocytes (p < 0.001), an effect qualitatively similar to that previously reported for WKY cardiomyocytes. Contractile function ofSHR cardiomyocytes cultured without sympathetic explants was 25% less than that of WKY cells (p < 0.005), but the response of SHR cardiomyocytes to sympathetic innervation was twice as great as that of WKY myocytes (p < 0.01). Cross-strain innervation experiments showed that sympathetic neurons from both strains were equally effective; interstrain differences were confined to the cardiomyocytes. Interstrain differences in cardiomyocyte contractile function and contractile response to sympathetic innervation are present before the onset of hypertension, and may in part account for alterations in cardiac function observed in prehypertensive SHR.

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