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Aging differentially affects direct and indirect actions of endothelin‐1 in perfused mesenteric arteries of the rat
Author(s) -
Dohi Yasuaki,
Lüscher Thomas F.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14110.x
Subject(s) - endocrinology , endothelin receptor , medicine , endothelin 1 , nitric oxide , endothelium , mesenteric arteries , acetylcholine , vasodilation , blood vessel , vascular smooth muscle , endothelins , circulatory system , contractility , inhibitory postsynaptic potential , chemistry , biology , artery , smooth muscle , receptor
1 The effects of age on the vascular action of endothelin‐1 were studied in mesenteric resistance arteries of 4,9 and 27 month old Fischer 344 rats. 2 Third order branches (about 200 μ m in diameter) of mesenteric resistance arteries were dissected free and mounted on glass cannulae in organ chambers. Changes in intraluminal diameter of the perfused and pressurized vessels were continuously measured with a video dimension analyzer. 3 Endothelin‐1 (10 −14 −3 × 10 −8 m .) caused contractions that were augmented after removal of the endothelium. The inhibitory effects of the endothelium were greater in young than in old rats. 4 The sensitivity of vascular smooth muscle to endothelin‐1 decreased with age, while the maximal response was maintained. In contrast, the contractions to noradrenaline were unaffected by aging. 5 Threshold concentrations of endothelin‐1 potentiated the contractions evoked by low and moderate concentrations of noradrenaline (10 −7 −10 −6 m ) in old, but not in young, rats. 6 Endothelium‐dependent relaxations to acetylcholine inhibited maximal contractions to endothelin‐1 and this effect decreased with age. In contrast, the relaxations to the nitric oxide donor, 3‐morpholinosydnonimine (SIN‐1; the active metabolite of molsidomine), did not differ in the three age groups. 7 Aging specifically decreases the direct contractile effects of endothelin‐1 and the inhibitory effects of the endothelium against these contractions, while the indirect (potentiating) effects of the peptide become more pronounced.