Effects of BQ-123 on systemic and renal hemodynamic responses to endothelin-1 in the rat split hydronephrotic kidney.
OBJECTIVE
To assess the site of action of endothelin-1 in vessels of different sizes in the kidney in vivo and investigate the function of endothelin A (ET(A)) receptors in mediating renal and systemic vasoconstriction.


METHODS
The luminal diameters of different vessels were measured and glomerular blood flow in cortical glomeruli was determined by intravital videomicroscopy in the split hydronephrotic kidney of anesthetized female Wistar rats.


METHODS
The rats were infused with endothelin-1 (40 pmol/kg per min) with or without pretreatment with the selective ET(A)-receptor antagonist BQ-123 (0.5 mg/kg). Aortic clamping was used to control renal blood pressure during the endothelin-1 infusion.


RESULTS
Exogenous endothelin-1 induced a significant rise (30+/-3%) in mean arterial pressure and a marked, long-lasting fall in glomerular blood flow (53+/-3%) related to reduction of the inner diameter of arcuate (-30%), interlobular arteries (-33%) and afferent arterioles (-17%). Aortic clamping to normalize renal blood pressure did not attenuate the vasoconstriction and reduction in glomerular blood flow. Pretreatment with BQ-123 significantly reduced both the endothelin-1-induced rise in mean arterial pressure (12+/-1%) and the fall in glomerular blood flow (-23+/-11%). BQ-123 blunted the response to endothelin-1 in arcuate (-12%), interlobular (-11%) and afferent vessels (-5%). Acetylcholine and nitroprusside completely reversed the vasoconstriction in BQ-123-pretreated animals.


CONCLUSIONS
BQ-123 largely prevented the hemodynamic effects of exogenously administered endothelin-1. Our direct in-vivo techniques showed that ET(A) receptors are, at least in part, involved in endothelin-1 -mediated vasoconstriction in the rat kidney, and support the hypothesis that ET(A) receptors may help to control arterial pressure in anesthetized rats.
Cavarape
A
A
Department of Internal Medicine, University of Udine, Italy. alessandro.cavarape@dpmsc.uniud.it
Bartoli
E
E
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006869:Hydronephrosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D018715:Microscopy, Video; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D014665:Vasodilator Agents; C072247:cyclo(Trp-Asp-Pro-Val-Leu)