Sanguinarine downregulates AT1a 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 d sanguinarine 0.1 mg/kg (SangL) and 0.3 mg/kg (SangH), losartan 1 mg/kg by weight (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 anesthetized (sodium thiopentane, 50 mg/kg), blood samples for aldosterone levels were taken, and kidneys were removed for AT1a mRNA expression. Los and SangH groups showed reduced AT1a mRNA expressions by 4.22- and 5.9-fold, respectively. 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 systolic blood pressure of 12.3% and 19.3%, respectively, whereas in the SangL group, it was reduced by 8.07%. Urine output in the Los group increased (228% mean increase from days 0-14), whereas sodium excretion decreased by 69.6% (mean decrease from days 0-14). In the SangL and SangH groups, urine volumes increased significantly by 108.3% and 115% (mean increase from days 0-14), respectively. Urinary sodium excretion increased significantly by 60.9% in the SangH group. We concluded that sanguinarine reduces blood pressure in the Dahl rat because of 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.
Singh
Ravesh
R
Pfizer Molecular Biology Research Facility, Nelson R Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South Africa.
Mackraj
Irene
I
Naidoo
Richard
R
Gathiram
Prem
P
D000450:Aldosterone / Q000097:blood; D000470:Alkaloids / Q000494:pharmacology* / Q000633:toxicity; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000494:pharmacology* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012964:Sodium / Q000652:urine
D000470:Alkaloids; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; C005705:sanguinarine