Angiotensin-converting enzyme and angiotensin II receptor subtype 1 inhibitors restitute hypertensive internal anal sphincter in the spontaneously hypertensive rats.

The present study determined the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril and angiotensin II receptor subtype 1 (AT1-R) antagonist losartan on the internal anal sphincter pressures (IASP) in spontaneously hypertensive rats (SHR) versus normotensive Wistar-Kyoto rats (WKY). The SHR had significantly higher IASP (21.7 +/- 0.8 mm Hg) than the WKY (14.7 +/- 0.9 mm Hg), which was associated with the higher levels of angiotensin II (Ang II) in plasma (50.3 +/- 0.9 pg/ml) and in muscle bath perfusates (72.7 +/- 11.8 pg/ml) compared with the WKY (p < 0.05). Captopril and losartan decreased the IASP in SHR and WKY, but they were more potent in SHR. Captopril and losartan normalized the IASP in the SHR, whereas these agents may compromise rectoanal continence in the WKY. Reverse transcriptase-polymerase chain reaction and Western blots showed higher levels of angiotensinogen, renin, ACE, and AT1-R in the internal anal sphincter (IAS) of SHR. Ang II caused concentration-dependent contraction of IAS smooth muscle strips from WKY (pEC50 = 8.5 +/- 0.1) and SHR (pEC50 = 8.6 +/- 0.2). Losartan (100 nM) significantly (p < 0.05) inhibited this effect. From these data, we conclude that 1) hypertensive IAS in SHR is primarily the result of renin-angiotensin system up-regulation, 2) ACE inhibitors and AT(1)-R antagonists simply relieve the hypertensive IAS, and 3) the differential effect of these inhibitors in the hypertensive versus the normotensive IAS may explain the lack of incontinence as a side effect in hypertensive patients receiving ACE inhibitors and AT1-R antagonists.

De Godoy MA ，Rattan S 《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》

Losartan reduces the increased participation of cyclooxygenase-2-derived products in vascular responses of hypertensive rats.

Alvarez Y ，Pérez-Girón JV ，Hernanz R ，Briones AM ，García-Redondo A ，Beltrán A ，Alonso MJ ，Salaices M ... -  《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》

Angiotensin II type 2 receptors contribute to vascular responses in spontaneously hypertensive rats treated with angiotensin II type 1 receptor antagonists.

Cosentino F ，Savoia C ，De Paolis P ，Francia P ，Russo A ，Maffei A ，Venturelli V ，Schiavoni M ，Lembo G ，Volpe M ... -  《AMERICAN JOURNAL OF HYPERTENSION》

Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats.

Kirimura K ，Takai S ，Jin D ，Muramatsu M ，Kishi K ，Yoshikawa K ，Nakabayashi M ，Mino Y ，Miyazaki M ... -  《HYPERTENSION RESEARCH》

Translocation of AT1- and AT2-receptors by higher concentrations of angiotensin II in the smooth muscle cells of rat internal anal sphincter.

de Godoy MA ，Rattan S 《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》