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Titolo:
sGC and PDE5 are elevated in lambs with increased pulmonary blood flow andpulmonary hypertension
Autore:
Black, SM; Sanchez, LS; Mata-Greenwood, E; Bekker, JM; Steinhorn, RH; Fineman, JR;
Indirizzi:
Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA Northwestern Univ Chicago IL USA 60611 Dept Pediat, Chicago, IL 60611 USA Northwestern Univ, Sch Med, Dept Mol Pharmacol, Chicago, IL 60611 USA Northwestern Univ Chicago IL USA 60611 l Pharmacol, Chicago, IL 60611 USA Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USAMassachusetts Gen Hosp Boston MA USA 02114 Res Ctr, Boston, MA 02114 USA Harvard Univ, Sch Med, Boston, MA 02114 USA Harvard Univ Boston MA USA 02114 vard Univ, Sch Med, Boston, MA 02114 USA Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USAUniv Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
fascicolo: 5, volume: 281, anno: 2001,
pagine: L1051 - L1057
SICI:
1040-0605(200111)281:5<L1051:SAPAEI>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; VASCULAR ENDOTHELIAL-CELLS; GENE-EXPRESSION; FETAL LAMBS; VASORELAXATION; RELAXATION; MANAGEMENT; ARTERY; LUNGS;
Keywords:
phosphodiesterase type 5; soluble guanylate cyclase; circulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Black, SM Northwestern Univ, Sch Med, Dept Pediat, Ward 12-191,303 E Chicago Ave, Chicago, IL 60611 USA Northwestern Univ Ward 12-191,303 E Chicago Ave Chicago IL USA 60611
Citazione:
S.M. Black et al., "sGC and PDE5 are elevated in lambs with increased pulmonary blood flow andpulmonary hypertension", AM J P-LUNG, 281(5), 2001, pp. L1051-L1057

Abstract

Utilizing aortopulmonary vascular graft placement, we established a lamb model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. We previously demonstrated that endothelial nitric oxide synthase (eNOS) is increased in lambs at age 4 wk. However, these lambs display a selective impairment of endothelium-dependent pulmonary vasodilation that is suggestive of a derangement downstream of NO release. Thus our objective was to characterize potential alterations in the expression and activity of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5) induced by increased pulmonary blood flow and pulmonary hypertension. Late-gestational fetal lambs (n = 10) underwent in utero placement of an aortopulmonary vascular graft (shunt). Western blotting analysis on lung tissue from 4-wk-old shunted lambs and age-matched controls showed thatprotein for both subunits of sGC was increased in shunted lamb lungs compared with age-matched controls. Similarly, cGMP levels were increased in shunted lamb lungs compared with age-matched controls. However, PDE5 expression and activity were also increased in shunted lambs. Thus although cGMP generation was increased, concomitant upregulation of PDE5 expression and activity may have (at least partially) limited and accounted for the impairmentof endothelium-dependent pulmonary vasodilation in shunted lambs.

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Documento generato il 31/03/20 alle ore 19:36:22