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      Effect of H-8, an Isoquinolinesulfonamide Inhibitor of Cyclic Nucleotide-Dependent Protein Kinase, on cAMP- and cGMP-Mediated Vasorelaxation

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          We theorized that H-8, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, an inhibitor of cyclic nucleotide-dependent protein kinases, might be a useful probe to assess cyclic nucleotide-dependent relaxation of blood vessels. However, working in the rat caudal artery and aorta, we found that neither cyclic AMP- nor cyclic GMP-mediated relaxations were diminished by even large doses of H-8. For example, in the caudal artery, relaxation of a phenylephrine contraction by 8-bromo-cGMP (10<sup>–5</sup> M) was unaffected by H-8: control, 33 ± 6.2%; 10 µ M H-8, 41 ± 12%; 30 µ M H-8, 30 ± 16% (p NS). The amount of relaxation by 8-bromo-cAMP (3 × 10<sup>–4</sup> M) was actually increased by H-8: control, 29 ± 7.6%; 10 µ M H-8, 34 ± 7.4%; 30 µ M H-8, 80 ± 14%. In the rat aorta, H-8 also failed to diminish relaxation induced by 8-bromo-cGMP, or by atriopeptin II or sodium nitroprusside. In both caudal artery and aorta, H-8 of itself caused a dose-dependent suppression of α-adrenergic contraction: for example, in the caudal artery, with 10 or 30 µ M H-8, peak contraction to phenylephrine was reduced to 70 (SEM) ± 12% or 52 ± 7% of control, respectively. The results suggest that the protein kinase inhibitor H-8 is not a useful probe to study cyclic nucleotide-dependent relaxation.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          23 September 2008
          : 28
          : 5
          : 366-371
          Department of Medicine, University of Illinois at Chicago School of Medicine and Westside V.A. Medical Center, Chicago, Ill.; Department of Physiology, Loyola University School of Medicine, Maywood, Ill, USA
          158883 Blood Vessels 1991;28:366–371
          © 1991 S. Karger AG, Basel

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          Pages: 6
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