Ouabain at nanomolar concentration promotes synthesis and release of angiotensin II from the endothelium of the tail vascular bed of spontaneously hypertensive rats.
The effects of 1 nM ouabain (OUA) on the contractile actions of phenylephrine (PHE, 0.001-100 microg) and functional activity of the sodium pump (NKA) in isolated-perfused tail vascular beds from WKY and SHR were investigated. In preparations from SHR, perfusion with OUA in the presence of endothelium (E+) increased the sensitivity (pED50) of PHE (before: 2.14 +/- 0.06 versus after: 2.47 +/- 0.07; P < 0.05) without altering the maximal response (Emax). After endothelial damage, OUA reduced the Emax of PHE in SHR (before: 350 +/- 29 versus after: 293 +/- 25 mm Hg; P < 0.05). In SHR/E+, pretreatment with losartan (10 microM) or enalaprilat (1 microM) prevented the increased sensitivity to PHE induced by OUA. OUA increased NKA activity in SHR/E+ (before: 45 +/- 6 versus after: 58 +/- 5%, P < 0.05). Losartan (10 mg/Kg, i.v.) also abolished the increment in systolic and diastolic blood pressure induced by OUA (0.18 microg/Kg, i.v.) in anesthetized SHR. OUA did not alter the actions of PHE in either anesthetized WKY rats or vascular preparations. Results suggest that 1 nM OUA increased the vascular reactivity to PHE only in SHR/E+. This effect is mediated by OUA-induced activation of endothelial angiotensin converting enzyme that promotes the local formation of angiotensin II, which sensitizes the vascular smooth muscle to the actions of PHE.
Padilha
Alessandra Simão
AS
Department of Physiological Sciences, Federal University of Espirito Santo, Sao Paulo, SP, Brazil.
Rossoni
Luciana Venturini
LV
Xavier
Fabiano Elias
FE
Vassallo
Dalton Valentin
DV
D000804:Angiotensin II / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015773:Enalaprilat / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000737:chemistry; D018738:Hexamethonium / Q000494:pharmacology; D007275:Injections, Intravenous; D019808:Losartan / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010042:Ouabain / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013623:Tail / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D014325:Tromethamine / Q000008:administration & dosage / Q000737:chemistry; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
C074097:Krebs-Henseleit solution; D014325:Tromethamine; D000804:Angiotensin II; D010656:Phenylephrine; D018738:Hexamethonium; D010042:Ouabain; D011189:Potassium Chloride; D000254:Sodium-Potassium-Exchanging ATPase; D015773:Enalaprilat; D005947:Glucose; D019808:Losartan