Afferent arteriolar vasodilation to the sulfonimide analog of 11, 12-epoxyeicosatrienoic acid involves protein kinase A. Hypertension 1999 Jan;33(1 Pt 2):408-13
Date
02/04/1999Pubmed ID
9931138DOI
10.1161/01.hyp.33.1.408Scopus ID
2-s2.0-0032942665 (requires institutional sign-in at Scopus site) 94 CitationsAbstract
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 micromol/L norepinephrine, averaged 18+/-1 microm (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 micromol/L H-89 (n=7) or 5 micromol/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 micromol/L histone H2B (n=5) or 10 micromol/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.
Author List
Imig JD, Inscho EW, Deichmann PC, Reddy KM, Falck JRMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic Acid8-Bromo Cyclic Adenosine Monophosphate
Animals
Arterioles
Cyclic AMP-Dependent Protein Kinases
Cyclic GMP
Cyclic GMP-Dependent Protein Kinases
Enzyme Inhibitors
Guanylate Cyclase
Histones
In Vitro Techniques
Isoquinolines
Juxtaglomerular Apparatus
Kidney Medulla
Kinetics
Male
Microscopy, Video
Muscle, Smooth, Vascular
Nephrons
Norepinephrine
Oxadiazoles
Protein Kinases
Quinoxalines
Rats
Rats, Sprague-Dawley
Renal Circulation
Sulfonamides
Vasodilation