title: Calcium dependence of effects of endothelin on rat mesenteric microvessels.
abstract: We investigated the calcium dependence of the effects of endothelin (ET) on resistance vessels (less than 300 microns lumen diameter) from the mesenteric vascular bed of the rat, mounted on a wire myograph. ET-1 induced a potent sustained contraction with an ED50 of 12 nmol/L. The response to ET-3 and big ET at the maximum concentrations used (100 nmol/L) was less than 40% of that to ET-1, with an estimated ED50 of 45 nmol/L. Relaxation of the ET-1-induced contraction was slow, and resulted in a reduction of the maximum response to a second challenge with ET-1 to 60% of the initial contraction after 3 h. Long-lasting tachyphylaxis to arginine vasopressin (AVP) induced contraction also occurred. The response to 100 nmol/L ET-1 produced an active tension 88% greater than that induced by 124 mmol/L KCl, and similar to that produced by norepinephrine and AVP. The response to 100 nmol/L ET-1 in the absence of calcium + 1 mmol/L EGTA in the medium for 30 min resulted in a maximum contraction of 43% of the response in the presence of calcium, followed by a faster relaxation rate. The addition of calcium produced a further contraction, and stimulation with 100 nmol/L ET-1 at this point did not result in further response. The calcium channel blocker nitrendipine in concentrations of 1-10 mumol produced increasing reductions of the responses to 100 nmol/L ET-1 to 35% at the higher concentration. Nitrendipine (3 mumol/L) partially blocked the response to calcium after ET-1 was added in the absence of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Clinical Research Institute of Montréal, Qué., Canada.
authors.forename: L Y
authors.initials: LY
authors.lastname: Deng
authors.forename: E L
authors.initials: EL
authors.lastname: Schiffrin
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002122:Calcium Chloride / Q000494:pharmacology; D002196:Capillaries / Q000187:drug effects; D019332:Endothelin-1; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects; D013618:Tachyphylaxis / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D001127:Arginine Vasopressin; D009568:Nitrendipine; D002122:Calcium Chloride; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine