Evidence for enhanced inhibitory modulation by cyclooxygenase products of noradrenergic neurotransmission in the mesenteric vasculature of young spontaneously hypertensive rats.
The effects of cyclooxygenase inhibition by indomethacin and meclofenamate on pre- and postjunctional aspects of noradrenergic neurotransmission were determined in mesenteric vascular preparations from 4- to 6-week-old spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). Perfusion pressure responses to periarterial nerve stimulation and to exogenous norepinephrine (NE) were significantly greater in SHR than in WKY preparations, whereas fractional NE overflow was equivalent between the two strains. Indomethacin and meclofenamate enhanced perfusion pressure responses to periarterial nerve stimulation in both strains. Fractional NE overflow was significantly enhanced by indomethacin but only at 14 Hz in SHR preparations, whereas it was unaffected in WKY preparations. The combination of indomethacin and cocaine resulted in a significant enhancement of perfusion pressure responses to periarterial nerve stimulation in both strains that was significantly greater than that produced by either drug alone. This effect was significantly greater in SHR than in WKY preparations. This combination also resulted in a significant enhancement of responses to exogenous NE in both strains. Fractional NE overflow was significantly increased in SHR preparations in the presence of the combination of cocaine and indomethacin, whereas it remained unaltered in WKY preparations. These findings suggest that a cyclooxygenase product exerts both pre- and postjunctional inhibitory effects on vascular noradrenergic neurotransmission that differ in these two strains of rats. The prejunctional inhibitory effect of this cyclooxygenase product was observed only in SHR preparations and was especially evident in the presence of cocaine.
Luthin
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Department of Pharmacology, Southern Illinois University School of Medicine, Springfield.
Cline
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WH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000201:enzymology / Q000294:innervation*; D009469:Neuromuscular Junction / Q000502:physiology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D010477:Perfusion; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016861:Cyclooxygenase Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D011453:Prostaglandins; D008469:Meclofenamic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D003042:Cocaine; D009638:Norepinephrine; D007213:Indomethacin