Role of protein kinase G in nitric oxide deficiency-induced supersensitivity to nitrovasodilator in rat pulmonary artery

Praveen K. Gupta, Jaganathan Subramani, Thakur Uttam Singh, Marie Dennis Leo, Anurag S. Sikarwar, Vellanki Ravi Prakash, Santosh K. Mishra

Research output: Contribution to journalArticle

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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 G -nitro-L-arginine methyl ester (1-NAME) treatment or endothelium removal on the vasodilator potency of SNP Sodium nitroprusside was more potent (pD 2 ; 8.21 ± 0.04) in relaxing arterial rings treated with 100μM L-NAME or denuded of the endothelium (pD 2 ; 8.44 ± 0.11) compared with the endothelium-intact controls (pD 2 ; 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 (pD 2 ; 5.04 ± 0.09) or endothelium removal (pD 2 ; 5.28 ± 0.11) in comparison with the controls (pD 2 ; 4.22 ± 0.17). On the other hand, dibutyryl cAMP, an activator of protein kinase A, was equipotent in dilating control (pD 2 ; 4.14 ± 0.04) and L-NAME-treated (pD 2 4.21 ± 0.05) vessels. Further, L-NAME treatment significantly (P ≤ 0.05) decreased the basal cGMP but enhanced SNP (1 μM)-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.

Original languageEnglish (US)
Pages (from-to)450-456
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume51
Issue number5
DOIs
StatePublished - May 1 2008
Externally publishedYes

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Cyclic GMP-Dependent Protein Kinases
NG-Nitroarginine Methyl Ester
Pulmonary Artery
Nitroprusside
Nitric Oxide
Endothelium
Vascular Smooth Muscle
Cyclic Nucleotides
Cyclic AMP-Dependent Protein Kinases
Vasodilator Agents
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Role of protein kinase G in nitric oxide deficiency-induced supersensitivity to nitrovasodilator in rat pulmonary artery. / Gupta, Praveen K.; Subramani, Jaganathan; Singh, Thakur Uttam; Leo, Marie Dennis; Sikarwar, Anurag S.; Prakash, Vellanki Ravi; Mishra, Santosh K.

In: Journal of Cardiovascular Pharmacology, Vol. 51, No. 5, 01.05.2008, p. 450-456.

Research output: Contribution to journalArticle

Gupta, Praveen K. ; Subramani, Jaganathan ; Singh, Thakur Uttam ; Leo, Marie Dennis ; Sikarwar, Anurag S. ; Prakash, Vellanki Ravi ; Mishra, Santosh K. / Role of protein kinase G in nitric oxide deficiency-induced supersensitivity to nitrovasodilator in rat pulmonary artery. In: Journal of Cardiovascular Pharmacology. 2008 ; Vol. 51, No. 5. pp. 450-456.
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AU - Gupta, Praveen K.

AU - Subramani, Jaganathan

AU - Singh, Thakur Uttam

AU - Leo, Marie Dennis

AU - Sikarwar, Anurag S.

AU - Prakash, Vellanki Ravi

AU - Mishra, Santosh K.

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N2 - 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 G -nitro-L-arginine methyl ester (1-NAME) treatment or endothelium removal on the vasodilator potency of SNP Sodium nitroprusside was more potent (pD 2 ; 8.21 ± 0.04) in relaxing arterial rings treated with 100μM L-NAME or denuded of the endothelium (pD 2 ; 8.44 ± 0.11) compared with the endothelium-intact controls (pD 2 ; 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 (pD 2 ; 5.04 ± 0.09) or endothelium removal (pD 2 ; 5.28 ± 0.11) in comparison with the controls (pD 2 ; 4.22 ± 0.17). On the other hand, dibutyryl cAMP, an activator of protein kinase A, was equipotent in dilating control (pD 2 ; 4.14 ± 0.04) and L-NAME-treated (pD 2 4.21 ± 0.05) vessels. Further, L-NAME treatment significantly (P ≤ 0.05) decreased the basal cGMP but enhanced SNP (1 μM)-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.

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