Factors influencing vascular hyporesponsiveness to angiotensin II.
Bartter's syndrome is characterized, in part, by hyporesponsiveness to the pressor effect of exogenous angiotensin II (AII). This has been attributed to volume contraction, hypokalemia, and/or increased prostaglandin (PG) levels. In order to investigate factors responsible for a diminished response to the pressor effect of AII, rats were made hypokalemic or volume contracted and hypokalemic (VCHK) by dietary restriction. AII sensitivity was examined by determining the dose of AII required to raise the mean arterial pressure 20 mm Hg. When compared with control rats. VCHK and hypokalemic rats were significantly less sensitive to AII. VCHK rats were significantly less sensitive to AII than hypokalemic rats. Both experimental groups were similarly hypokalemic, but plasma renin activity (PRA) of VCHK only was greater than control values. In VCHK rats, acute K+ restoration partially corrected AII hyporesponsiveness, although plasma K+ increased to normal. In VCHK rats, acute volume expansion with normal saline similarly achieved only partial correction of AII hyporesponsiveness although PRA values fell to the control range. Simultaneous K+ restoration and volume expansion to VCHK rats successfully restored AII sensitivity to the control range. Dietary sodium, chloride, and potassium restriction did not increase urinary excretion to PGE2. Indomethacin (5 mg/kg, iv) given acutely to VCHK rats did not significantly after baseline hyporesponsiveness to AII. Norepinephrine vascular sensitivity was not affected by either volume contraction or hypokalemia. These data demonstrate that volume contraction and hypokalemia individually depress exogenous AII sensitivity in the rat and do so by separate and additive mechanisms. Furthermore, these mechanisms appear to be independent of PG.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume; D007008:Hypokalemia / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D011458:Prostaglandins E; D000804:Angiotensin II; D011188:Potassium; D009638:Norepinephrine