AT1 receptor blockade prevents the increase in blood pressure and the augmentation of intrarenal ANG II levels in hypertensive Cyp1a1-Ren2 transgenic rats fed with a high-salt diet.
BACKGROUND
This study was performed to determine the effects of high-salt diet on the magnitude of the increases in systolic blood pressure (SBP) and kidney tissue angiotensin (ANG) II levels that occur after induction of ANG II-dependent malignant hypertension in Cyp1a1-Ren2 transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)].


METHODS
Cyp1a1-Ren2 rats (n = 6) were fed a normal diet containing 0.3% indole-3-carbinol (I3C) for 10 days to induce ANG II-dependent malignant hypertension.


RESULTS
Rats induced with I3C exhibited increases in SBP and elevations of ANG II levels in kidney cortex and medulla. In a second group of rats (n = 6), high-salt intake alone did not alter basal SBP; however, subsequent dietary administration of 0.3% I3C during continued high-salt intake elicited a substantially greater increase in SBP than observed in rats fed a normal salt diet. ANG II levels in kidney cortex and medulla of rats induced with I3C and fed a high-salt diet were elevated similarly to those in rats induced with I3C alone. Chronic administration of the AT1 receptor antagonist, losartan (100 mg/L in drinking water, n = 6), markedly attenuated the I3C-induced increase in SBP and prevented the augmentation of ANG II levels in kidney cortex and medulla in rats induced with I3C and maintained on a high-salt diet.


CONCLUSIONS
Activation of AT1 receptors contributes to the augmented blood pressure and elevated kidney tissue ANG II levels that occur in Cyp1a1-Ren2 transgenic rats with malignant hypertension maintained on a high-salt diet.
Williams
Dustyn E
DE
Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Prieto
Minolfa C
MC
Mullins
John J
JJ
Navar
L Gabriel
LG
Mitchell
Kenneth D
KD
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics*; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D051381:Rats; D055647:Rats, Transgenic; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism* / Q000502:physiology; D012083:Renin / Q000096:biosynthesis / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; C473112:Ren2 protein, mouse; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D019363:Cytochrome P-450 CYP1A1; D012083:Renin; D019808:Losartan