Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that the effects of angiotensin II type 1 receptor (AT1R) blockers are in part because of angiotensin II type 2 receptor (AT2R) signaling. Interactions between the AT2R and kinins modulate cardiovascular function. Because AT2R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT1R blocker valsartan and the ACE inhibitor benazepril require AT2R signaling through the bradykinin 1 and 2 receptors (B1R and B2R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT2R inhibitor), valsartan+des-arg9-[Leu8]-bradykinin (B1R inhibitor), valsartan+HOE140 (B2R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT2R, B1R, or B2R in the presence of valsartan prevented the reduction seen with valsartan alone. B2R blockade inhibited the effect of benazepril. Injury increased AT1R, AT2R, B1R, and B2R expression. Treatment with valsartan but not benazepril significantly increased intima AT2R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT2R, B1R, and B2R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT2R, B1R, and B2R. Results suggest that AT2R expression and increased cGMP represent a molecular mechanism that differentiates AT1R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril.
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PMID:Angiotensin II type 2 receptor expression after vascular injury: differing effects of angiotensin-converting enzyme inhibition and angiotensin receptor blockade. 1698 65

The objective of the present study was to examine further the underlying mechanism of the antihypertensive effect of the total flavonoid (TF), extracted from the seed of Astragalus complanatus R.Brown. Renovascular hypertension rats (RHR) were established by the two-kidney one clip (2K1C) method. The effect of TF on the contraction of portal vein was studied in an isolated preparation. The response of portal vein to angiotensin II (Ang II) was expressed as a percentage of the 100 mmol/l KCl induced maximum contraction. We took the dose-response curve of portal vein to Ang II (from 10(-9) to 10(-6) mmol/l) as the control and then observed the change of curve after TF and Valsartan (Ang II receptor blocker) administration. Ang II induced a concentration-dependent increase of the contraction amplitude (maximal increase, 46.53+/-5.15% of 100 mmol/l KCl induced contraction at Ang II 10(-6) mmol/l in RHR). The Ang II-induced portal vein contraction was prevented by TF with a concentration related manner (maximal inhibition amplitude from 46.53+/-5.15% to 22.525+/-4.67% of 100 mmol/l KCl contraction at 10(-6)mmol/l Ang II and 3.12 x 10(-1) mg/l TF in RHR). The effect of TF on Ang II-induced portal vein contraction was similar to Valsartan. These results showed that the antihypertensive action of TF was attributed to the dilation of vessels and is related to the blockade of the Ang II receptor.
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PMID:Effect of total flavonoid fraction of Astragalus complanatus R. Brown on angiotensin II-induced portal-vein contraction in hypertensive rats. 1840 89