Role of c-jun n-terminal kinase in the regulation of vascular tone

Ming Sheng Zhou, Ivonne Hernandez Schulman, Kiranmai Chadipiralla, Leopoldo Raij

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The c-Jun N-terminal kinases (JNKs) belong to the mitogen-activated protein kinases superfamily, which play an important role in the pathogenesis of cardiovascular and metabolic diseases. However, it is still unclear whether JNK participates in the regulation of vascular tone. We investigated the effect of JNK inhibitors on vascular reactivity in aortic rings in organ bath and on angiotensin (Ang) II-induced pressor responses in vivo in Sprague-Dawley (SD) rats. In aortic rings from SD rats, KCl, norepinephrine (NE), Ang II, or endothelin 1 (ET)-1 induced a dose-dependent vasoconstriction. Preincubation with the JNK inhibitor SP600125 (20 μmol/L) slightly inhibited KCl-induced vasoconstriction (Emax: -19%) and markedly inhibited vasoconstriction to NE (-42%), Ang II (-54%), and ET-1 (-42%). SP600125 induced a dose-dependent relaxation in the NE-preconstricted aortic rings (-54%) but exerted minimal relaxation in the KCI-preconstriction rings. To exclude the nonspecific effect of SP600125, we performed additional experiments using JNK peptide inhibitor 1, L-stereoisomer (L-JNKI1), a cell-permeable peptide inhibitor specific for JNK. Compared to SP600125, L-JNKI1 (20 μmol/L) had a smaller but still significant inhibitory effect on NE-induced vasoconstriction (-18%) and did not inhibit KCI-induced vasoconstriction. Next, we investigated the effect of L-JNKI1 (5 mg/kg intravenously [IV]) in vivo on Ang II-induced pressor responses in SD rats. Ang II induces a dose-dependent increase in systolic blood pressure and L-JNKI1 slightly attenuated the Ang II-induced pressor response. These results suggest that JNK signaling plays a role in the regulation of vascular tone.

Original languageEnglish (US)
Pages (from-to)78-83
Number of pages6
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume15
Issue number1
DOIs
StatePublished - Mar 1 2010

Keywords

  • Angiotensin II
  • Endothelium
  • Hypertension

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine

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