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

Academic Article

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.
  • Authors

    Published In

  • Hypertension  Journal
  • Author List

  • Imig JD; Inscho EW; Deichmann PC; Reddy KM; Falck JR
  • Start Page

  • 408
  • End Page

  • 413
  • Volume

  • 33
  • Issue

  • 1 II