title: Role of protein kinase G in nitric oxide deficiency-induced supersensitivity to nitrovasodilator in rat pulmonary artery.
abstract: The aim of the present study was to examine the role of protein kinase G (G-kinase) in the mechanism of endogenous nitric oxide (NO) deficiency-induced supersensitivity to the nitrovasodilator sodium nitroprusside (SNP) in isolated rat pulmonary artery. Tension experiments and cGMP measurements were carried out on isolated rat pulmonary artery to assess the influence of NO deficiency, caused by either N-nitro-L-arginine methyl ester (L-NAME) treatment or endothelium removal on the vasodilator potency of SNP. Sodium nitroprusside was more potent (pD2; 8.21 +/- 0.04) in relaxing arterial rings treated with 100microM L-NAME or denuded of the endothelium (pD2; 8.44 +/- 0.11) compared with the endothelium-intact controls (pD2; 7.61 +/- 0.05). Similarly, the tissue sensitivity to 8-Br-cGMP, a G-kinase activator, was significantly (P < 0.05) greater after L-NAME treatment (pD2; 5.04 +/- 0.09) or endothelium removal (pD2; 5.28 +/- 0.11) in comparison with the controls (pD2; 4.22 +/- 0.17). On the other hand, dibutyryl cAMP, an activator of protein kinase A, was equipotent in dilating control (pD2; 4.14 +/- 0.04) and L-NAME-treated (pD2 4.21 +/- 0.05) vessels. Further, L-NAME treatment significantly (P < 0.05) decreased the basal cGMP but enhanced SNP (1 microM)-stimulated increase in the tissue cyclic nucleotide levels (271.8 +/- 39.93 pmol/mg protein versus control: 66.19 +/- 7.18 pmol/mg protein), indicating sensitization of soluble guanylyl cyclase to NO. The increased sensitivity of G-kinase to cGMP observed in the present study suggests a novel mechanism of supersensitivity in vascular smooth muscle to nitrovasodilators in acute NO deficiency. Further, it explains the influence of ambient cGMP in determining the sensitivity of G-kinase in vascular smooth muscle.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izzatnagar, Uttar Pradesh, India.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Gupta
authors.forename: Jaganathan
authors.initials: J
authors.lastname: Subramani
authors.forename: Thakur Uttam
authors.initials: TU
authors.lastname: Singh
authors.forename: Marie Dennis Marcus
authors.initials: MD
authors.lastname: Leo
authors.forename: Anurag S
authors.initials: AS
authors.lastname: Sikarwar
authors.forename: Vellanki Ravi
authors.initials: VR
authors.lastname: Prakash
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000172:deficiency / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester