Tags

Type your tag names separated by a space and hit enter

Angiotensin-converting enzyme and angiotensin II receptor subtype 1 inhibitors restitute hypertensive internal anal sphincter in the spontaneously hypertensive rats.
J Pharmacol Exp Ther. 2006 Aug; 318(2):725-34.JP

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College of Thomas Jefferson University, 1025 Walnut St., Room 901 College; Philadelphia, PA 19107, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16648368

Citation

De Godoy, Márcio A F., and Satish Rattan. "Angiotensin-converting Enzyme and Angiotensin II Receptor Subtype 1 Inhibitors Restitute Hypertensive Internal Anal Sphincter in the Spontaneously Hypertensive Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 318, no. 2, 2006, pp. 725-34.
De Godoy MA, Rattan S. Angiotensin-converting enzyme and angiotensin II receptor subtype 1 inhibitors restitute hypertensive internal anal sphincter in the spontaneously hypertensive rats. J Pharmacol Exp Ther. 2006;318(2):725-34.
De Godoy, M. A., & Rattan, S. (2006). Angiotensin-converting enzyme and angiotensin II receptor subtype 1 inhibitors restitute hypertensive internal anal sphincter in the spontaneously hypertensive rats. The Journal of Pharmacology and Experimental Therapeutics, 318(2), 725-34.
De Godoy MA, Rattan S. Angiotensin-converting Enzyme and Angiotensin II Receptor Subtype 1 Inhibitors Restitute Hypertensive Internal Anal Sphincter in the Spontaneously Hypertensive Rats. J Pharmacol Exp Ther. 2006;318(2):725-34. PubMed PMID: 16648368.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-converting enzyme and angiotensin II receptor subtype 1 inhibitors restitute hypertensive internal anal sphincter in the spontaneously hypertensive rats. AU - De Godoy,Márcio A F, AU - Rattan,Satish, Y1 - 2006/04/28/ PY - 2006/5/2/pubmed PY - 2006/9/1/medline PY - 2006/5/2/entrez SP - 725 EP - 34 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 318 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16648368/Angiotensin_converting_enzyme_and_angiotensin_II_receptor_subtype_1_inhibitors_restitute_hypertensive_internal_anal_sphincter_in_the_spontaneously_hypertensive_rats_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&amp;pmid=16648368 DB - PRIME DP - Unbound Medicine ER -