Experimental diabetes: reduction of serotonin-induced vasoconstriction by meclofenamic acid in vitro.
In diabetes the sensitivity of isolated rat aortae to serotonin is greatly diminished and the dose-response curve is shifted to the right. The maximal response is reduced to 37% of control, the threshold dose is approximately tenfold greater, and the ED50 is about fourfold greater than control. This decrease in sensitivity may be due, in part, to a reduction in the synthesis of prostaglandins because serotonin-induced responses in normal and diabetic arteries treated with meclofenamate are also significantly diminished. In addition, there is evidence that both receptor-operated Ca2+ and potential-operated Ca2+ channels may be impaired because the responses to norepinephrine and KCl are both dampened in diabetic aortae. The greatly diminished effect of serotonin may be a sensitive tool to study the nature of diabetes better and to monitor its development.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D062367:ortho-Aminobenzoates; D012701:Serotonin; D008469:Meclofenamic Acid; D011189:Potassium Chloride; D009638:Norepinephrine