Afferent arteriolar vasodilation to the sulfonimide analog of 11,12- epoxyeicosatrienoic acid involves protein kinase A

John D. Imig, Edward W. Inscho, Paul C. Deichmann, K. Malla Reddy, John R. Falck

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

The current study determined the contribution of protein kinase-A (PKA) and protein kinase-G (PKG) to the vasodilation elicited by the N- methylsulfonimide analog of 11,12-epoxyeicosatrienoic acid (11,12-EET). Experiments were performed, in vitro, using the juxtamedullary nephron preparation combined with videomicroscopy. The response of afferent arterioles to the sulfonimide analog of 11,12-EET, was determined before and after inhibition of PKA, PKG, or guanylyl cyclase. Afferent arterioles, preconstricted with 0.5 μmol/L norepinephrine, averaged 18±1 μm (n=25) at a renal perfusion pressure of 100 mm Hg. Superfusion with 0.01 to 100 nmol/L of the 11,12-EET analog caused a graded increase in diameter of the afferent arteriole. Vessel diameter increased by 11±1% and 15±1%, respectively, in response to 10 and 100 nmol/L of the 11,12-EET analog. The afferent arteriolar response to 10 and 100 nmol/L of the 11,12-EET analog was significantly attenuated during inhibition of PKA with 10 μmol/L H-89 (n=7) or 5 μmol/L myristolated PKI (n=6), such that afferent arteriolar diameter increased by only 5±2% and 2±1%, respectively, in response to 100 nmol/L of the 11,12-EET analog. In contrast, the afferent arteriolar vasodilatory response to the 11,12-EET analog was unaffected by PKG or guanylyl cyclase inhibition. In the presence of 200 μmol/L histone H2B (n=5) or 10 μmol/L ODQ (n=7), the afferent arteriolar diameter increased by 16±3% and 12±2%, respectively, in response to 100 nmol/L of the 11,12-EET analog. These results demonstrate that activation of PKA is an important mechanism responsible for the afferent arteriolar vasodilation elicited by the sulfonimide analog of 11,12-EET.

Original languageEnglish (US)
Pages (from-to)408-413
Number of pages6
JournalHypertension
Volume33
Issue number1 II
DOIs
StatePublished - Jan 1999

Keywords

  • Arterioles
  • Cyclic adenosine monophosphate
  • Cyclic guanosine monophosphate
  • Endothelium-derived hyperpolarizing factor
  • Kidney
  • Metabolites, cytochrome P450

ASJC Scopus subject areas

  • Internal Medicine

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