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Titolo:
CYP4A1 antisense oligonucleotide reduces mesenteric vascular reactivity and blood pressure in SHR
Autore:
Wang, MH; Zhang, F; Marji, J; Zand, BA; Nasjletti, A; Laniado-Schwartzman, M;
Indirizzi:
New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA New York Med Coll Valhalla NY USA 10595 Pharmacol, Valhalla, NY 10595 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
fascicolo: 1, volume: 280, anno: 2001,
pagine: R255 - R261
SICI:
0363-6119(200101)280:1<R255:CAORMV>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPONTANEOUSLY HYPERTENSIVE RATS; ARACHIDONIC-ACID METABOLISM; THICK ASCENDING LIMB; K+ CHANNEL; CYTOCHROME-P-450; INHIBITORS; GENES; TONE; SUBFAMILY; ARTERIES;
Keywords:
20-hydroxyeicosatetraenoic acid; phenylephrine; myogenic response; kidney; blood pressure;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Laniado-Schwartzman, M New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA New York Med Coll Valhalla NY USA 10595 10595 USA
Citazione:
M.H. Wang et al., "CYP4A1 antisense oligonucleotide reduces mesenteric vascular reactivity and blood pressure in SHR", AM J P-REG, 280(1), 2001, pp. R255-R261

Abstract

The cytochrome P-450 4A (CYP4A)-derived arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) affects renal tubular and vascular functions and has been implicated in the control of arterial pressure. We examined the effect of antisense oligonucleotide (ODN) to CYP4A1, the low K-m arachidonic acid omega -hydroxylating isoform, on vascular 20-HETE synthesis,vascular reactivity, and blood pressure in the spontaneously hypertensive rat (SHR). Administration of CYP4A1 antisense ODN decreased mean arterial blood pressure from 137 +/- 3 to 121 +/- 4 mmHg (P < 0.05) after 5 days of treatment, whereas treatment with scrambled antisense ODN had no effect. Treatment with CYP4A1 antisense ODN reduced the level of CYP4A-immunoreactive proteins along with 20-HETE synthesis in mesenteric arterial vessels. Mesenteric arteries from rats treated with antisense ODN exhibited decreased sensitivity to the constrictor action of phenylephrine (EC50 0.69 +/- 0.17 vs.1.77 +/- 0.40 <mu>M). Likewise, mesenteric arterioles from antisense ODN-treated rats revealed attenuation of myogenic constrictor responses to increases of transmural pressure. The decreased vascular reactivity and myogenicresponses were reversible with the addition of 20-HETE. These data suggestthat CYP4A1-derived 20-HETE facilitates myogenic constrictor responses in the mesenteric microcirculation and contributes to pressor mechanisms in SHR.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 10:20:09