Alteration of response to neuropeptide Y in the nucleus tractus solitarius of spontaneously hypertensive rats.

Abstract

In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 ptnol) into the unilateral nucleus tractus solitarius elicited dose-dependent vasodepressor and bradycardic responses accompanied by an inhibition of sympathetic nerve firing. After microinjections of the a 2 -adrenergic receptor antagonist yohimbine (100 ng) into the nucleus tractus solitarius, the depressor and bradycardic responses to the injection of neuropeptide Y (25 pmol) into the nucleus tractus solitarius were significantly attenuated. In contrast, pretreatment with the a,-adrenergic receptor antagonist doxazosin (200 ng) injected into the nucleus tractus solitarius did not alter these responses. In spontaneously hypertensive rats, microinjections of neuropeptide Y (25 pmol) into the nucleus tractus solitarius also elicited depressor and bradycardic responses that were significantly less than those of normotensive Wistar-Kyoto rats. However, pretreatment with yohimbine (100 ng) in the nucleus tractus solitarius did not diminish these depressor responses in spontaneously hypertensive rats. Depressor responses to neuropeptide Y, which was administered after yohimbine pretreatment, were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. The results suggest that the depressor and bradycardic responses elicited by neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity. These responses may be mediated in part by a 2 -adrenergic receptor in the nucleus tractus solitarius. The impairment of a 2 -adrenergic receptor-mediated responses to neuropeptide Y in spontaneously hypertensive rats may contribute to the development of hypertension. 4 Thus, these findings suggest that NPY is involved in the central regulation of blood pressure. In in vitro studies, it has been demonstrated that NPY could interact with the a 2 -adrenergic receptor in the medulla oblongata and that this interaction could be impaired in spontaneously hypertensive rats (SHR). 5However, the underlying mechanism of action of NPY in the brain area has not been clarified.The present study was designed to determine the role of the a-adrenergic receptor in cardiovascular responses to NPY injected into the NTS in normotensive rats and SHR.

Neuropeptide Y and sympathetic control of vascular tone in hypertension

“…The depressor effect of Int NPY was significantly reduced when examined in 10-week-old SHR in contrast to WKY, Sprague Dawley or DOCA-salt hypertensive rats [69]. Injections of NPY into the NTS also induced a depressor effect that was also attenuated in SHR compared to WKY [72].…”

The Effect of Acute and Chronic Restraint on the Central Expression of Prepro‐Neuropeptide Y mRNA in Normotensive and Hypertensive Rats

“…The arcuate nucleus sends efferent projections that contain NPY to many nuclei involved in autonomic regulation, such as the PVN and NTS (44, 45). Within the PVN and NTS, NPY has direct and indirect effects on blood pressure (46–49). Moreover, the NPY system appears to be dysfunctional in SHR in these same regions, particularly in the NTS (32,47–50), suggesting that increased prepro‐NPY mRNA expression in the arcuate nucleus may contribute to neurochemical and functional deficits in regions implicated in cardiovascular control.…”

“…However, the present study has shown that chronic restraint induced a significant increase in prepro‐NPY mRNA expression in the NTS of SHR, while the expression of prepro‐NPY mRNA did not differ from basal levels in WKY rats exposed to chronic restraint. The implications of an increased expression of prepro‐NPY mRNA in the NTS are widespread, as microinjection of NPY into the NTS has resulted in hypotension, bradycardia, bradypnea and elevated plasma insulin levels (48, 49, 62–64). Furthermore, strain‐related differences in NPY neurochemistry and functional effects of NPY have been reported in the NTS of SHR compared to WKY (32).…”