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Role of nitric oxide in the contractile response to 5‐hydroxytryptamine of the basilar artery from Wistar Kyoto and stroke‐prone rats
Author(s) -
Salomone Salvatore,
Morel Nicole,
Godfraind Théophile
Publication year - 1997
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 - 10.1038/sj.bjp.0701227
Subject(s) - basilar artery , medicine , endocrinology , contraction (grammar) , nitric oxide , acetylcholine , cerebral arteries , chemistry , nitric oxide synthase , nitroarginine
Isolated basilar arteries from spontaneously hypertensive stroke‐prone rats (SHRSP) are more sensitive to the contractile effect of 5‐hydroxytryptamine (5‐HT) than those from normotensive Wistar Kyoto rats (WKY). This has been attributed to a different proportion of 5‐HT receptor subtypes mediating these responses. In the present study we have examined if differences in nitric oxide release could also contribute to this difference in sensitivity to 5‐HT. At rest, the normalized internal diameter was significantly smaller in SHRSP (297.4±3.5μm, n =88) than in WKY (375.1±4.0μm, n =62, P <0.01) arteries. The contractile response to 100m m KCl was higher in WKY (3.57±0.15mNmm −1 , n =22) than in SHRSP arteries (2.32±0.20mNmm −1 , n =28, P <0.01). When added on the plateau of contraction to 5‐HT (1μ m ), acetylcholine (ACh, 3μ m ) evoked significant relaxation in all preparations from WKY ( n =20), but only in 15 out of 26 preparations from SHRSP. The mean relaxations were 55.4±5.2% in WKY and 20.6±4.6% in SHRSP (as % of the contractile tone evoked by 5‐HT; P <0.01). The NO synthase inhibitor N ω ‐nitro‐ l ‐arginine ( l ‐NOARG, 0.1m m ) produced a similar increase in tone in both WKY and SHRSP. This tone was equal (in % of the contractile response to 100m m KCl) to 70.8±4.4% in WKY ( n =20) and 67.6±5.9% in SHRSP ( n =26) and was reversed by l ‐arginine (1m m ) and by 1,4‐dihydropyridine calcium channel blockers (10n m nisoldipine, 10n m lacidipine, 100n m nifedipine). The l ‐NOARG‐induced tone was absent when the arteries were bathed in phosphate‐free Krebs (pH7.4). EC 50 values of 5‐HT were about four fold smaller in SHRSP than in WKY arteries ( P <0.01). The maximal response to 5‐HT (E max ) was higher than 100m m KCl‐contraction in SHRSP but not in WKY arteries. Removal of endothelium produced a shift to the left of the 5‐HT curve in WKY, but not in SHRSP arteries. When evoked in phosphate‐free Krebs, the contractile responses to 5‐HT showed tachyphylaxis, but the responses were reproducible by adding the agonist at 30min intervals. In such conditions, EC 50 values of 5‐HT were about two fold smaller in SHRSP than in WKY arteries ( P <0.01). In phosphate‐free Krebs, the blockade of NO synthase did not change the contractile response to 100m m KCl; it reduced EC 50 and increased E max of 5‐HT in WKY, but not in SHRSP. These results confirm that the sensitivity to 5‐HT is higher in basilar artery isolated from SHRSP than in those from WKY. They show that endothelium‐dependent vasorelaxation to ACh is impaired in SHRSP. The finding that removal of endothelium or blockade of NO synthase augmented the contractile response to 5‐HT in WKY, but not in SHRSP basilar arteries indicates that the difference in responsiveness to 5‐HT observed between WKY and SHRSP basilar arteries might be, at least in part, related to dissimilarities in NO release. Furthermore, the l ‐NOARG‐induced contraction sensitive to calcium channel blockers indicates that, in basilar arteries, NO production might lower L‐type calcium channel opening and thereby control the tone of the vessels.