Atrial natriuretic peptide reverses afferent arteriolar vasoconstriction and potentiates efferent arteriolar vasoconstriction in the isolated perfused rat kidney.
The intrarenal sites of action of atrial natriuretic peptide (ANP) have not been resolved fully. Although ANP relaxes in vitro preparations of smooth muscle and exerts profound effects on renal hemodynamics, the effects of ANP on resistance vessels remain a subject of controversy. In the present study, we utilized an in vitro perfused hydronephrotic rat kidney model to assess directly the actions of ANP on renal microvessels during norepinephrine (NE)-induced renal vasoconstriction. Perfusion pressure was maintained constant, and perfusate flow to the kidney was monitored while the afferent arteriole (AA) and efferent arteriole (EA) were visualized using videomicroscopy. Renal AA and EA diameters were measured by computer-assisted image analysis. NE (0.3 microM) decreased renal perfusate flow from 11.8 +/- 1.7 (S.E.) to 5.8 +/- 1.2 ml/min (P less than .005), decreased AA diameter from 20.2 +/- 0.7 to 14.3 +/- 0.8 mu (P less than .005) and decreased EA diameter from 18.6 +/- 1.2 to 15.1 +/- 1.2 mu (P less than .005). ANP (human ANF-(4-28), anaritide, Wyeth) completely reversed the NE-induced AA vasoconstriction with an IC50 of 9.3 +/- 5.6 nM. In contrast, ANP caused a further decrease in EA diameter at concentrations up to 10(-8) M, and elicited a slight dilation of the EA at 10(-7) M. In normal rat kidneys perfused under identical conditions, NE decreased renal perfusate flow, glomerular filtration rate and filtration fraction. ANP increased glomerular filtration rate and filtration fraction above control levels, with maximal effects at 10(-8) M.(ABSTRACT TRUNCATED AT 250 WORDS)
Loutzenhiser
R
R
Nephrology Section, Veterans Administration Medical Center, Miami, Florida.
Hayashi
K
K
Epstein
M
M
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D005919:Glomerular Filtration Rate; D006869:Hydronephrosis / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D009320:Atrial Natriuretic Factor; D009638:Norepinephrine; D010646:Phentolamine