Sanguinarine alters AT1a cardiac and renal gene expression in a hypertensive rat model

We studied the in vivo effects of sanguinarine in a hypertensive rat model and its effects on AT1a mRNA expression in kidney tissues. Rats received, daily, for 14 days sanguinarine 0.1 mg/kg (SangL) and 0.3 mg/kg (SangH), losartan 1mg/kg b.w. (Los) or DMSO (Con). Blood pressures were monitored regularly and urine volume and sodium concentration was measured on days 0, 7 and 14. On day 15, animals were anaesthetized (sodium thiopentane, 50 mg/kg), blood samples for aldosterone levels were taken and kidneys removed for AT1a mRNA expression. Los and SangH groups showed reduced AT1a mRNA expressions by 4.22 and 5.9 fold, respectively. Gene expression was also altered in cardiac tissue in the treated groups. In the SangL group it was reduced by 2.7 fold. Decreases in systolic blood pressures mirrored decreases in AT1a mRNA expressions in all groups. Los and SangH groups showed reductions in SBP of 12.3 % and 19.3%, respectively, whilst in the SangL group it was reduced by 8.07%. Urine output in the Los group increased ( 228 % mean increase from Day 0 to 14) while sodium excretion decreased by 69.6 %. (mean decrease from Day 0 to 14). In the SangL and SangH groups urine volumes increased significantly by 108.3 % and 151 % (mean increase from Day 0 to 14), respectively. Urinary sodium excretions increased significantly by 60.9 % in the SangH group. We conclude that sanguinarine reduces blood pressure in the Dahl rat which is due to decreased AT1 receptor expression and reduced aldosterone levels. The action of losartan on increased urinary volume and decreased sodium excretion may be attributed to reduced vasopressin secretion.