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.

Abstract

INTRODUCTION:

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.

• Authors: Dustyn E Williams, Minolfa C Prieto, John J Mullins, L Gabriel Navar, Kenneth D Mitchell
• Journal: The American journal of the medical sciences (Am J Med Sci) Vol. 339 Issue 4 Pg. 356-61 (Apr 2010) ISSN: 1538-2990 [Electronic] United States
• PMID: 20224314 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antihypertensive Agents
• Receptor, Angiotensin, Type 1
• Ren2 protein, mouse
• Sodium Chloride, Dietary
• Angiotensin II
• Cytochrome P-450 CYP1A1
• Renin
• Losartan

Topics

• Angiotensin II (antagonists & inhibitors, biosynthesis)
• Angiotensin II Type 1 Receptor Blockers (pharmacology, therapeutic use)
• Animals
• Antihypertensive Agents (therapeutic use)
• Blood Pressure (drug effects, genetics)
• Cytochrome P-450 CYP1A1 (biosynthesis, genetics)
• Hypertension (drug therapy, genetics, physiopathology)
• Kidney (drug effects, enzymology, metabolism)
• Losartan (pharmacology, therapeutic use)
• Male
• Mice
• Rats
• Rats, Transgenic
• Receptor, Angiotensin, Type 1 (metabolism, physiology)
• Renin (biosynthesis, genetics)
• Sodium Chloride, Dietary (adverse effects)