Prolonged exposure to catecholamines enhances sensitivity of smooth muscle relaxation induced by sodium nitroprusside and atriopeptin.
Desensitization of alpha-1 adrenergic receptor-mediated contraction occurs in aortic smooth muscle from rats after in vitro exposure to norepinephrine (NE). The purpose of this study was to examine effects of pretreatment of blood vessels with catecholamines on relaxant responses of the vessels to sodium nitroprusside (SNP) and atriopeptin III (ANF). Vessels preincubated with NE for 4 hr had a markedly increased sensitivity to relaxation induced by SNP as compared to controls. The concentration of SNP giving half-maximal relaxation (log EC50) was -8.78 +/- 0.09 in the vessels pretreated with NE and -7.40 +/- 0.18 in controls (P less than .001). NE-treated vessels also had an increased sensitivity to ANF (EC50 -8.23 +/- 0.11 vs. -7.03 +/- 0.31, respectively; P less than .01). However, both desensitized and control vessels had similar sensitivity to relaxation induced by 8-bromo-cyclic GMP. The capacity of SNP to stimulate intracellular cyclic GMP accumulation in vessels pretreated with NE was greater than controls at a high concentration of SNP (10(-5) M.). However, there was no correlation between vasodilation induced by lower concentrations of SNP and stimulation of cyclic GMP accumulation in these blood vessels. Activity of soluble and particulate guanylate cyclase in NE-treated vessels was increased compared to controls. Changes in sensitivity of smooth muscle relaxation to SNP and ANF after prolonged exposure to catecholamines may relate to changes in capacity of the cyclic GMP system.
Department of Medicine, Stanford University School of Medicine, California.
Z W
ZW
Hu
K
K
Honda
F
F
Murad
B B
BB
Hoffman
D000818:Animals; D001011:Aorta / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010446:Peptide Fragments; D051381:Rats; D011919:Rats, Inbred Strains
D010446:Peptide Fragments; D009599:Nitroprusside; C062525:atrial natriuretic factor prohormone (103-126); C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP; D009638:Norepinephrine