Vascular chemical sulfhydryl alkylation in vitro: alterations in intracellular calcium and cAMP and cGMP metabolism.
This study examined the effect of N-ethylmaleimide (NEM, 10(-7) M) on agonist-induced contraction and the relaxation following drug-washout, of vascular smooth muscle (VSM) segments derived from hypertensive rabbits. Mean blood pressure increase was produced either by renal constriction plus contralateral nephrectomy, or by cadmium acetate ingestion. Freely-ionized calcium (45Ca)flux, cyclic 3':5'-guanosine monophosphate (cGMP), and cyclic 3':5' adenosine monophosphate (cAMP), were analyzed. NEM was used as a stereoselective probe to clarify the role of sulfhydryl (SH) groups in hypertension. Contractile response to norepinephrine (NE, 5.9 x 10(-7) M), angiotensin II (AT, 9.8 x 10(-8) M), and potassium chloride (KCl, 2.2 x 10(-2) M) were significantly depressed in hypertensive tissue. Exposure to NEM, before agonist challenge, caused an even greater depression in contractile response. As for the normotensive group, an inhibition of relaxation occurred when NEM was added after the development of a maximal contractile response to NE, AT or KCl. Changes in contractile ability and in relaxation were attributed to specific alterations in calcium distribution. These alterations were examined by 45Ca washout components and were related to cAMP and cGMP metabolism. These results suggest a regulatory role of SH groups in contraction and relaxation and a modification of this role in hypertension.
Tomera
J F
JF
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
D000085:Acetates / Q000633:toxicity; D000478:Alkylation; D000804:Angiotensin II / Q000493:pharmacokinetics; D000818:Animals; D002104:Cadmium / Q000633:toxicity; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D005033:Ethylmaleimide / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006977:Hypertension, Renal / Q000139:chemically induced / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000493:pharmacokinetics; D011189:Potassium Chloride / Q000493:pharmacokinetics; D011817:Rabbits; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000085:Acetates; D013439:Sulfhydryl Reagents; D002104:Cadmium; D000804:Angiotensin II; D011189:Potassium Chloride; C028031:cadmium acetate; D000242:Cyclic AMP; D006152:Cyclic GMP; D005033:Ethylmaleimide; D002118:Calcium; D009638:Norepinephrine