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Am J Physiol Renal Physiol (August 15, 2001). doi:10.1152/ajprenal.0157.2001
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Articles in PresS, published online ahead of print August 15, 2001
Am J Physiol Renal Physiol, 10.1152/ajprenal.0157.2001
Submitted on May 17, 2001
Accepted on July 24, 2001

Determinants of the renal microvascular response to acetylcholine, afferent and efferent arteriolar actions of EDHF

Xuemei Wang1 and Rodger Loutzenhiser1*

1 Smooth Muscle Reseach Group, University of Calgary, Calgary, Alberta, Canada

* To whom correspondence should be addressed. E-mail: rloutzen{at}ucalgary.ca.

ACh induced vasodilation of cortical afferent and efferent arterioles was investigated using the in vitro perfused hydronephrotic rat kidney. ACh reversed angiotensin II induced vasoconstriction in both the afferent and efferent arteriole (106±2% and 75±5% dilation at 10 µmol/L, respectively). Inhibition of nitric oxide synthase (NOS, 100 µmol/L L-NAME) and cyclooxygenase (COX, 10 µmol/L ibuprofen) blocked the sustained ACh response of the afferent arteriole, but did not affect the magnitude of the initial dilation (97±7% dilation). In contrast, NOS/COX inhibition completely abolished ACh-induced efferent arteriolar dilation. The mechanisms underlying the NOS/COX-independent actions of ACh on the afferent arteriole were characterized using K channel blockers. Tetraethylammonium (TEA) had no effect at 1 mmol/L, but attenuated the response at 10 mmol/L (35±5% dilation ). Barium (100 µmol/L) and ouabain (3 mmol/L) had no effect, arguing against a role of the inward rectifier K channel or Na/K ATPase. Charybdotoxin (ChTX, 10 nmol/L) and apamin (1.0 µmol/L) partially blocked the response when administered alone (63±% and 37±5% dilation, respectively) and abolished the response when co-administered (0.1±1.0% dilation). These findings indicate that the NO-independent effects of ACh on the renal microvasculature involve K channels that are sensitive to a combination of apamin and ChTX, but are insensitive to 1 mmol/L TEA or 100 µmol/L barium. This EDHF-like mechanism exerts a segmental-specific action, modulating preglomerular, but not post-glomerular tone, an observation that is consistent with the evolving concept that vasomotor mechanisms in the cortical efferent arteriole do not involve voltage-gated Ca entry.




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