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Analysis of the Effects of Graded Levels of Hypoxia on Noradrenaline‐Evoked Contraction in the Rat Iliac Artery in vitro
Author(s) -
Bartlett Iain S.,
Marshall Janice M.
Publication year - 2002
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/eph8702341
Subject(s) - contraction (grammar) , phenylephrine , tetraethylammonium , chemistry , endocrinology , medicine , agonist , hypoxia (environmental) , glibenclamide , vasoconstriction , depolarization , nicardipine , ketanserin , receptor , calcium , 5 ht receptor , potassium , serotonin , oxygen , blood pressure , organic chemistry , diabetes mellitus
In rings of rat iliac artery, contractions were evoked by noradrenaline (NA), the selective α 1 adrenoceptor agonist phenylephrine (PE), and K + , which causes depolarisation‐induced contraction. There was no evidence of α 2 adrenoceptor‐evoked contraction. Hypoxia, induced by reducing P O2 in the bath from 100 mmHg to 70, 55 or 40 mmHg, had similar effects on rings with (E+) and without (E‐) endothelium. In E‐ rings, the NA concentration‐response curve was biphasic, whereas that for PE was monophasic. Hypoxia reduced maximum contractions in response to NA and PE (NA max and PE max , respectively) without affecting the concentrations that evoked 50% of maximum contraction (EC 50 ). At P O2 of 70 mmHg, NA max of the high affinity α 1 receptor for NA (NA maxh ) and PE max were reduced by ∼15%, but at P O2 of 55 and 40 mmHg, NA maxh was severely attenuated while PE max fell by 45 and 75%, respectively. Similarly, the Ca 2+ channel blocker nicardipine depressed NA maxh and PE max , but P O2 of 55 mmHg further reduced NA max and PE max . Hypoxia also reduced contractions evoked by NA, PE or K + at the concentrations required to produce 80% of the maximum contraction (EC 80 ), receptor‐mediated contractions being more affected. Ca 2+ ‐free conditions reduced the contractions evoked by NA and PE, at the EC 80 , to ∼10% of control. The K + channel inhibitors glibenclamide and tetraethylammonium did not prevent hypoxia‐induced depression of PE‐evoked contraction. Thus, contractions evoked in iliac artery by the high affinity subtype of α 1 adrenoceptor for NA, which may respond to circulating levels of NA, and by the single α 1 adrenoceptor subtype for PE, are especially vulnerable to P O2 levels ≤ 55 mmHg. We propose that this reflects hypoxia‐induced inhibition of Ca 2+ influx through L‐type and receptor‐operated Ca 2+ channels; K + channel opening makes little contribution.