Enhanced myogenic response in the afferent arteriole of spontaneously hypertensive rats

Ren Y, D'Ambrosio MA, Liu R, Pagano PJ, Garvin JL, Carretero OA. Enhanced myogenic response in the afferent arteriole of spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 298: H1769-H1775, 2010. First published April 2, 2010; doi:10.1152/ajpheart.00537.2009.-Spontaneously hypertensive rats (SHRs) have normal glomerular capillary pressure even though renal perfusion pressure is higher, suggesting that preglomerular vessels exhibit abnormally high resistance. This may be due to increased superoxide (O-2(-)) production, which contributes to the vasoconstriction in hypertension. We tested the hypothesis that the myogenic response of the afferent arteriole (Af-Art) is exaggerated in SHRs because of increased levels of reactive oxygen species (ROS). Single Af-Arts were microdissected from kidneys of SHRs and Wistar-Kyoto (WKY) rats and microperfused in vitro. When perfusion pressure in the Af-Art was increased stepwise from 60 to 140 mmHg, the luminal diameter decreased by 8.4 +/- 2.9% in WKY Af-Arts but fell by 29.3 +/- 5.6% in SHR Af-Arts. To test whether ROS production is enhanced during myogenic response in SHRs, we measured chloromethyl-dichlorodihydrofluorescein diacetate acetyl ester (CM-H(2)DCFDA) florescence before and after increasing intraluminal pressure from 60 to 140 mmHg. Pressure-induced increases in ROS were fourfold greater in SHR Af-Arts compared with WKY Af-Arts (SHR, 48.0 +/- 2.2%; and WKY, 12.2 +/- 0.3%). To test whether O-2(-) contributes to the myogenic response in SHRs, either the membrane-permeant O-2(-) scavenger Tempol or the nox2-based NADPH oxidase (NOX2) inhibitor gp91ds-tat were added to the Af-Art lumen and bath and the myogenic response was tested before and after treatment. Both Tempol (10(-4) M) and gp91ds-tat (10(-5) M) significantly attenuated the pressure-induced constriction in SHR Af-Arts but not in WKY Af-Arts. We conclude that 1) pressure-induced constriction is exaggerated in SHR Af-Arts, 2) NOX2-derived O-2(-) may contribute to the enhanced myogenic response, and 3) O-2(-) exerts little influence on the myogenic response under normotensive conditions.