Studies on blood pressure regulation in hypertensive ren-2 transgenic rats.
Transgenic rats harboring the mouse ren-2 gene develop severe hypertension in association with suppressed kidney and plasma renin levels. Extra-renal expression of the ren-2 gene occurs in a number of sites, and is particularly high in the adrenal cortex. We have investigated the response of blood pressure and heart rate in ren-2 rats to acute converting enzyme inhibition and to sodium depletion. In response to a single dose of captopril (1 mg/kg i.p.), blood pressure in ren-2 rats was rapidly normalized, whereas normotensive Sprague-Dawley rats were relatively unresponsive to captopril. In response to the sodium depletion protocol (five days on low-sodium diet, with furosemide administered on day 1) both ren-2 rats and normotensive Sprague-Dawley rats underwent similar initial losses of sodium followed by a gradual return to net sodium balance. Diastolic pressure in ren-2 rats fell from 160 +/- 9 mm Hg to 105 +/- 10 mm Hg after 72 hours, whereas blood pressure in Sprague-Dawley rats was essentially unchanged. The response to captopril implies a major role for angiotensin II in sustaining hypertension, and this may result from tissue generation of angiotensin I. The response to sodium depletion suggests a volume-dependent component, which may result from elevated aldosterone levels, possibly due to enhanced adrenal renin expression.
Barrett
G L
GL
AFRC Centre for Genome Research, University of Edinburgh, Scotland, United Kingdom.
Mullins
J J
JJ
D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000235:genetics / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D002216:Captopril; D012964:Sodium; D012083:Renin