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Titolo:
Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1receptor effects on renal bradykinin and cGMP
Autore:
Siragy, HM; de Gasparo, M; El-Kersh, M; Carey, RM;
Indirizzi:
Univ Virginia Hlth Syst, Charlottesville, VA USA Univ Virginia Hlth Syst Charlottesville VA USA , Charlottesville, VA USA
Titolo Testata:
HYPERTENSION
fascicolo: 2, volume: 38, anno: 2001,
pagine: 183 - 186
SICI:
0194-911X(200108)38:2<183:AEIPAI>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIC GUANOSINE 3',5'-MONOPHOSPHATE; CONGESTIVE-HEART-FAILURE; NITRIC-OXIDE; PROSTAGLANDIN E(2); CONSCIOUS RATS; INTERSTITIAL BRADYKININ; DOWN-REGULATION; BLOOD-PRESSURE; BLOCKADE; VASODILATION;
Keywords:
angiotensin-converting enzyme inhibitors receptors, angiotensin II; bradykinin; rats; cyclic GMP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Siragy, HM Univ Virginia, Hlth Sci Ctr, Dept Med, 1300 Jefferson Pk Ave, Charlottesville, VA 22908 USA Univ Virginia 1300 Jefferson Pk Ave Charlottesville VA USA 22908
Citazione:
H.M. Siragy et al., "Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1receptor effects on renal bradykinin and cGMP", HYPERTENSIO, 38(2), 2001, pp. 183-186

Abstract

Angiotensin (Ang) receptor blockers (ARBs) increase bradykinin (BK) by antagonizing Ang II at its type 1 (AT(1)) receptors and diverting Ang II to its counterregulatory type 2 (AT(2)) receptors. Because the effect of ARBs onBK is constrained by the short half-life of BK and because ACE inhibitors block the degradation of BK, this study was designed to test the hypothesisthat an ACE inhibitor can potentiate ARB-induced increases in renal interstitial fluid (RIF) BK levels. We used a microdialysis technique to recover BK and cGMP in vivo from the RIF of sodium-depleted, conscious Sprague-Dawley rats infused for 60 minutes with the AT(1) receptor blocker valsartan (0.17 mg/kg per minute), with the active metabolite of the ACE inhibitor benazepril (benazeprilate, 0.05 mg/kg per minute), or with the specific AT(2) receptor blocker PD 123,319 (50 mug/kg per minute) alone or combined. Each animal served as its own control. RIF BK and cGMP levels increased significantly over I hour in response to valsartan, benazeprilate, or both but not to a vehicle control (P<0.01). The combined benazeprilate-valsartan effect was greater than the sum of their individual effects, suggesting potentiation rather than addition, and was abolished by PD 123,319. We demonstrate forthe first time that an ACE inhibitor (benazepril) and an ARB (valsartan) potentiate each other, and we postulate that such combinations may be beneficial in clinical states marked by Ang II elevation, such as chronic heart failure, postinfarction left ventricular dysfunction, and hypertension.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/10/20 alle ore 18:18:35