Effect of Chronically Administered Hydralazine on Altered Adrenergic Neurotransmission Mediated by Presynaptic α-and β-Adrenoceptors in Spontaneously Hypertensive Rats

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The effects of chronically administered hydralazine on adrenergic neurotransmission were evaluated in the perfused mesenteric artery of spontaneously hypertensive rats (SHR) preloaded with [^3H] norepinephrine. The ^3H overflow evoked by periarterial nerve stimulation (PNS, 2-32Hz) was greater in both young (5-week-old) and adult (13-week-old) ages of SHR in comparison with agematched Wistar Kyoto rats (WKY). Hydralazine treatment, which prevented the development of hypertension, attenuated the increased ^3H overflow evoked by PNS in SHR. At adult age, the logarithmic value for the concentration (nM) of salbutamol to cause a 20% enhancement of the evoked ^3H overflow was significantly smaller in SHR than in WKY. The increased sensitivity of presynaptic β-adrenoceptors in SHR was reduced by hydralazine treatment. The concentration-response curve of the facilitation of the evoked ^3H overflow caused by salbutamol in hydralazine-treated SHR lay between the curves in SHR and WKY. No significant difference in the inhibitory effects of xylazine on the PNS-evoked ^3H overflow was found among SHR, hydralazine-treated SHR and WKY. At young age, presynaptic α- and β-adrenoceptors were supersensitive in SHR. The results suggest that an altered adrenergic neurotransmission mediated by presynaptic β-adrenoceptors in adult SHR is partially improved by chronic hydralazine administration, this accounting for the attenuation of the increased norepinephrine release observed in hydralazine-treated SHR.
公益社団法人日本薬学会の論文

Effect of Chronically Administered Hydralazine on Altered Adrenergic Neurotransmission Mediated by Presynaptic α-and β-Adrenoceptors in Spontaneously Hypertensive Rats

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