Area-specific differences in transmitter release in central catecholaminergic neurons of spontaneously hypertensive...

The link among blood pressure, sympathetic output, and brain neurons producing catecholamines is well documented. Nevertheless, their intrinsic properties and any alterations in signaling characteristics between normotensive and hypertensive phenotypes remain unknown. Here, we directly compared neurophysiological properties of catecholamine release of C1 and A2 neurons of the spontaneously hypertensive rat and Wistar rat in organotypic slices. C1 and A2 areas were studied because both are widely implicated in the pathophysiology of hypertension. Catecholaminergic neurons were visualized using viral vectors to express green fluorescent protein. Microamperometry revealed that C1 axonal varicosities of spontaneously hypertensive but not normotensive Wistar rats release a transmitter predominantly (approximately 86%) in very large quanta, comparable in catecholamine load to adrenal chromaffin granules. Because quantal size affects the spread of transmitter in the extracellular space, this may enhance the impact of C1 varicosities on their downstream targets and increase sympathetic drive in the hypertensive rat. Electrophysiological properties and Ca2+ handling were studied using patch clamp and confocal imaging. Although overall electrophysiological characteristics of C1 and A2 neurons were comparable between strains, the characteristic angiotensin-II-induced Ca2+ mobilization was reduced in A2 neurons of the spontaneously hypertensive rat. Because A2 neurons are a part of a homeostatic antihypertensive circuit, this could reduce their restraining influence on blood pressure. Thus, we have revealed an increased quantal size in C1 varicosities and a reduced responsiveness of A2 neurons of the spontaneously hypertensive rat to angiotensin II. Both effects could contribute to elevated sympathetic activity and blood pressure in the spontaneously hypertensive rat.