The vasoconstriction induced by endothelin-1 is mediated only by ET(A) receptors in mesenteric small resistance arteries of spontaneously hypertensive rats and Wistar Kyoto rats.
OBJECTIVE
To evaluate the functional responses of mesenteric small resistance arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rat controls to endothelin-1 (ET-1), in the presence and absence of an ET(A) receptor antagonist drug as well as to an ET(B) receptor agonist.


METHODS
Twenty rats aged 12 weeks were studied. They were 10 SHR and 10 WKY rats. Mesenteric small resistance arteries (relaxed diameter 100-180 microm) were dissected and mounted on a micromyograph (Mulvany's technique). A dose-response curve for response to ET-1 was plotted for cumulative concentrations (from 10(-11) to 10(-8) mol/l) in the presence and absence of 10(-6) mol/l FR 139317 (a selective antagonist of ET(A) receptors). In addition, the effects of 10(-7) mol/l N-succinyl-[Glu9, Ala11,15]-endothelin 1 fragment 8-21 (IRL 1620, a selective agonist of ET(B) receptors) were evaluated.


RESULTS
The response of ET-1 was greater in WKY rats than it was in SHR. Almost all the vasoconstrictor effect of ET-1 could be prevented by addition of FR 139317, whereas the agonist of ET(B) receptors had no effect (no change in active force).


CONCLUSIONS
The contractile effects of ET-1 on mesenteric small resistance arteries of SHR and WKY rats are mediated mostly by ET(A) receptors, whereas ET(B) receptors play a minor role, if any. It is possible, however, that a vasoconstrictor effect of ET(B) receptors on the smooth muscle could be masked by the concomitant stimulation of endothelial ET(B) vasodilator receptors.
Rizzoni
D
D
Cattedra di Semeiotica e Metodologia Medica, U.O.P. Scienze Mediche, University of Brescia, Italy.
Porteri
E
E
Piccoli
A
A
Castellano
M
M
Bettoni
G
G
Pasini
G
G
Agabiti-Rosei
E
E
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D001381:Azepines; D019332:Endothelin-1; D016232:Endothelins; D007211:Indoles; D010446:Peptide Fragments; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C074308:sovateltide; C079574:FR 139317