Stimulation of AT2 receptor exerts beneficial effects in stroke-prone rats: focus on renal damage
2009 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 27, no 12, 2444-2451 p.Article in journal (Refereed) Published
Background and aim Angiotensin II acts through two major receptors: AT1-R and AT2-R. It is known that the stimulation of AT1-R mediates vasoconstriction, cell proliferation and fibrosis, aldosterone release and inflammatory response but, although the stimulation of AT2-R is thought to promote vasodilation and anti-inflammatory effects, its real in-vivo functions are still unclear. The aim of this study was to investigate the effects of specific and selective AT2-R stimulation on the pathological events occurring in spontaneously hypertensive stroke-prone rats (SHRSPs). Methods and results SHRSPs who were fed a high-salt diet underwent long-term treatment with vehicle or compound 21 (C21), a nonpeptide selective AT2-R agonist, at doses of 0.75, 5 and 10 mg/kg per day. The vehicle-treated rats developed brain abnormalities detectable by magnetic resonance imaging after 42.5 +/- 7.5 days, and died 43 +/- 9.5 days after the start of the dietary treatment. The highest C21 dose delayed the occurrence of brain damage (P<0.001 vs. vehicle-treated SHRSPs) and prolonged survival (P<0.001) without affecting blood pressure. These beneficial effects of C21 were abolished by the administration of PD123319, an AT2-R antagonist. C21 treatment preserved renal structure by preventing inflammatory cell infiltration, collagen accumulation, and the neo-expression of vimentin; it also prevented the increased plasma renin activity and accumulation of urinary acute-phase proteins observed in the vehicle-treated rats. Conclusion Specific and selective AT2-R stimulation has beneficial effects on the pathological events occurring in SHRSPs. These data indicate a new avenue for the pharmacological treatment of diseases in which modulation of the renin-angiotensin system is required.
Place, publisher, year, edition, pages
2009. Vol. 27, no 12, 2444-2451 p.
angiotensin type 2 receptor, fibrosis, inflammation, kidney, stroke-prone rats
Research subject Organic Pharmaceutical Chemistry
IdentifiersURN: urn:nbn:se:uu:diva-124922DOI: 10.1097/HJH.0b013e3283311ba1ISI: 000272420800020OAI: oai:DiVA.org:uu-124922DiVA: diva2:318168