Enhanced Renal Sympathetic and Cardiovascular Responses to Substance P in Hypertension

Blood pressure, heart rate, and renal sympathetic nerve responses were measured in 9-13 week old male spontaneously hypertensive rats (SHR) and compared to those in age and sex-matched Wistar-Kyoto (WKY) rats following intravenous injection of the neuropeptide substance P (SP), the nicotinic stimulant 1,1-dimethyl-4-phenylpiperazinium (DMPP), and the adrenoceptor stimulant norepinephrine (NE). Charles River Sprague-Dawley (CD) rats were used in some studies to develop methodologies. Measurements were made in control rats and also following sinoaortic denervation, pithing, ganglion blockade, or adrenoceptor blockade. Responses were evaluated in order to determine if ganglion stimulation by SP was enhanced in SHR compared to WKY rats and if this enhancement was selective for SP or would also be exhibited to DMPP. NE was used to evaluate adrenergic sensitivity and to confirm the success of baroreceptor denervations. SHR exhibited greater intrinsic sympathetic tone than WKY rats before and following ganglion blockade. Ganglion stimulation by SP and DMPP was only fully revealed following elimination of baroreceptor input. Results indicated that SP stimulates sympathetic ganglia to increase renal sympathetic nerve activity, heart rate and blood pressure in CD, SHR and WKY rats. This increase was enhanced in SHR compared to WKY rats in the absence of a similar enhancement of responses to DMPP. The action of SP to cause vasodilation was attenuated in SHR versus WKY rats which may augment its action as a pressor agent in SHR. In conclusion, increases in blood pressure, heart rate and renal sympathetic nerve activity were selectively increased to SP in SHR versus WKY rats. This enhanced action of SP may contribute to the elevation of basal and/or evoked sympathetic discharge observed in this model of hypertension