The interaction between noradrenaline and ATP upon polyphosphoinositide metabolism and contraction in tail arteries from normo- and hypertensive rats.
The effects of, and interaction between, noradrenaline and alpha,beta-methylene ATP upon polyphosphoinositide (PPI) breakdown, investigated by measuring the accumulation of inositol phosphates, and contraction, were studied in tail arteries from normo- (WKY) and spontaneously-hypertensive (SHR) rats. Noradrenaline (10(-7)-10(-3) M) evoked a prazosin (10(-6) M)-sensitive, concentration-dependent increase in total inositol phosphate accumulation in both WKY and SHR rats. No significant differences were observed in either the maximal response or in the concentration range over which noradrenaline evoked this response, between these two populations. Noradrenaline (5 x 10(-7)-5 x 10(-5) M) evoked a concentration-dependent contraction of arteries from both SHR and WKY rats. The responses to noradrenaline were about 2-fold greater at all effective concentrations of noradrenaline in SHR compared with WKY rats. alpha,beta-Methylene ATP (10(-6) M) did not alter noradrenaline-stimulated total inositol phosphate accumulation, in arteries from either SHR or WKY rats, measured either as the maximal response or as the EC50. alpha,beta-Methylene ATP (5 x 10(-6) M), by itself, evoked a contractile response, which was quantitatively similar in SHR and WKY rats, and was additive with the contractile responses to noradrenaline (5 x 10(-7)-5 x 10(-5) M). The maximum response produced by a combination of noradrenaline and alpha,beta-Methylene ATP was quantitatively similar to that produced by noradrenaline alone. No evidence of synergism between alpha,beta-Methylene ATP and noradrenaline upon contraction was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Glasgow, UK.
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Guild
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Jenkinson
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Muir
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000032:analysis; D009638:Norepinephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D000255:Adenosine Triphosphate; D009638:Norepinephrine; D011224:Prazosin