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Titolo:
Increased coronary effects of stimulation of endothelin-B receptor in experimental hypercholesterolemia
Autore:
Mathew, V; Miller, VM; Hasdai, D; Barber, DA; Holmes, DR; Lerman, A;
Indirizzi:
Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn Rochester MN USA 55905 Dis, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn, Dept Internal Med, Rochester, MN 55905 USA Mayo Clin& Mayo Fdn Rochester MN USA 55905 Med, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn, Dept Surg & Physiol, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn Rochester MN USA 55905 siol, Rochester, MN 55905 USA
Titolo Testata:
CORONARY ARTERY DISEASE
fascicolo: 8, volume: 11, anno: 2000,
pagine: 585 - 592
SICI:
0954-6928(200012)11:8<585:ICEOSO>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
A RECEPTOR; CELLULAR BIOLOGY; FLOW VELOCITY; VASOCONSTRICTION; ANTAGONIST; ARTERIES; ET(B); ATHEROSCLEROSIS; RESISTANCE; BLOCKADE;
Keywords:
endothelin; sarafotoxin; endothelin receptor; endothelin-derived relaxing factor; coronary circulation; hypercholesterolemia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Mathew, V Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn 200 1st St SW Rochester MN USA 55905 05 USA
Citazione:
V. Mathew et al., "Increased coronary effects of stimulation of endothelin-B receptor in experimental hypercholesterolemia", CORON ART D, 11(8), 2000, pp. 585-592

Abstract

Background Vasoconstriction in response to endothelin-l has been shown to be primarily related to its effects on the endothelin-A receptor, Experimental hypercholesterolemia is associated with an increase in coronary vasoconstrictor response to endothelin-1 in vivo, although the relative contributions of subtypes of endothelin receptor in this model remain unknown,Objective To test the hypothesis that there is an increase in coronary vasoconstriction in response to stimulation of endothelin-B receptor in hypercholesterolemia, which might be related to attenuation of activity of endothelin-derived relaxing factor. Methods We infused 5 ng/kg/min sarafotoxin, a specific endothelin-B receptor agonist, or 50 mug/kg/min NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase, into the left anterior descending coronary arteries of pigs before and after feeding them a cholesterol-rich diet for 10 weeks. Results There was a significant increase in serum level of cholesterol. After 10 weeks, infusion of sarafotoxin resulted in an accentuated decrease in coronary blood flow (CBF) compared with baseline (decreases by 60 +/- 7 versus 34 +/- 6%, P < 0.05), There was no significant difference between theeffects on diameter of coronary arteries for the two time periods, The effect of L-NMMA on CBF was attenuated after 10 weeks (by 5 +/-10.1 versus 45.6 +/- 4.7%, P < 0.05), Endothelin-receptor status of epicardial coronary arteries remained unchanged. Sarafotoxin and L-NMMA were cc-infused at the above-mentioned doses into normolipidemic animals; the decrease in CBF in response to this cc-infusion was comparable to the decrease observed with sarafotoxin alone in hypercholesterolemic animals (decreases of 67 +/- 5 versus60 +/- 7, NS),Conclusions The present results demonstrate that selective stimulation of the endothelin-B receptor increases coronary vasoconstriction in experimental hypercholesterolemia, primarily at the level of the microvasculature. These findings may be related to the attenuation of activity of endothelin-derived relaxing factor in this model, and support the hypothesis that endothelin-B receptor plays a role in the regulation of coronary vascular tone inpathophysiologic states. Coron Artery Dis 11:585-592 (C) 2000 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 06:25:21