Effect of chronically administered hydralazine on altered adrenergic neurotransmission mediated by presynaptic alpha- and beta-adrenoceptors in spontaneously hypertensive rats.
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, 2-32 Hz) was greater in both young (5-week-old) and adult (13-week-old) ages of SHR in comparison with age-matched 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 beta-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 alpha- and beta-adrenoceptors were supersensitive in SHR. The results suggest that an altered adrenergic neurotransmission mediated by presynaptic beta-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.
Takata
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Mochizuki
S
S
Kato
H
H
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation / Q000648:ultrastructure; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013599:Systole / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014316:Tritium; D014991:Xylazine / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D017981:Receptors, Neurotransmitter; D014316:Tritium; D006830:Hydralazine; D014991:Xylazine; D009638:Norepinephrine