The role of intrarenal angiotensin II in the development of hypertension in Ren-2 transgenic rats.
OBJECTIVE
We investigated the responses of mean arterial pressure and renal blood flow to intravenous and intrarenal angiotensin II, plasma and kidney angiotensin II concentrations and renal angiotensin receptor subtype 1 protein expression, and renal functional responses to intravenous and intrarenal angiotensin receptor 1 blockade with candesartan.


METHODS
In male anaesthetized transgenic rats and Hannover Sprague-Dawley rats aged 36-38 days mean arterial pressure and renal blood flow were determined after intravenous and intrarenal boluses of angiotensin II. Mean arterial pressure, renal blood flow and sodium excretion after intravenous or intrarenal candesartan were studied. Plasma and kidney angiotensin II concentrations were determined by radioimmunoassay. Renal angiotensin receptor subtype 1 protein levels were analysed by immunoblotting.


RESULTS
The responses of mean arterial pressure and renal blood flow to angiotensin II were significantly greater in transgenic than in Hannover Sprague-Dawley rats. The administration of candesartan resulted in comparable decreases in mean arterial pressure and increases in renal blood flow and sodium excretion in both groups of rats. Renal angiotensin receptor subtype 1 protein levels were no different between Hannover Sprague-Dawley and transgenic rats.


CONCLUSIONS
Plasma and kidney angiotensin II levels were lower in anaesthetized transgenic rats but, in contrast, were higher in decapitated transgenic rats when compared with Hannover Sprague-Dawley rats, suggesting that the kidney function of prehypertensive transgenic rats is under inappropriately high angiotensin II-dependent influence.
Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Libor
L
Kopkan
Herbert J
HJ
Kramer
Zuzana
Z
Husková
Zdenka
Z
Vanourková
Petra
P
Skaroupková
Monika
M
Thurmová
Ludek
L
Cervenka
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000737:chemistry*; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013777:Tetrazoles / Q000494:pharmacology
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011506:Proteins; D013777:Tetrazoles; D000804:Angiotensin II; D012964:Sodium; C081643:candesartan