A functional study of the development of the cardiac sympathetic neuroeffector junction in the SHR

We studied the function of the cardiac sympathetic nerve varicosity in isolated right atrial preparations of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 4, 9, 14, 20 and 50 weeks of age. Cumulative concentration-atrial period response (C-R) curves to isoprenaline showed similar maximum response and sensitivity (EC50) at all ages but there was an age-related fall in resting atrial rate. Similar results were found for methoxamine (alpha 1-adrenoceptor agonist) although the maximum response was significantly less than for isoprenaline. The time-dependent recovery (T 1/2) of the fall in atrial period in response to sympathetic nerve stimulation from electrical field pulses (1-32 at 1 Hz) was enhanced by neuronal uptake inhibition by desipramine (0.1-1 mumol/l), to a similar degree at all ages. Pre-junctional alpha 2-adrenoceptor stimulation by clonidine caused progressively more inhibition of the number of field pulses-fall in period relationship with age. SHR atria were similar to WKY rat atria at all ages except for a further impairment of the development of pre-junctional alpha 2-adrenoceptors. These studies indicate that the function of the cardiac sympathetic varicosity matures early (by 4 weeks) and overall there is very little impairment in SHR versus WKY rat atria.