Effect of nitro-L-arginine on electrical and mechanical responses to acetylcholine in the superior mesenteric artery from stroke-prone hypertensive rat
P. Ghisdal et al., Effect of nitro-L-arginine on electrical and mechanical responses to acetylcholine in the superior mesenteric artery from stroke-prone hypertensive rat, BR J PHARM, 128(7), 1999, pp. 1513-1523
1 High salt diet is known to aggravate the vascular pathology in spontaneou
sly hypertensive stroke-prone rats (SHR-SP). The aim of the present study w
as to assess the involvement of endothelial dysfunction in this effect. Con
tractile tension and membrane potential were simultaneously recorded in sup
erior mesenteric artery rings of untreated and NaCl-loaded (1% NaCl in the
drinking water) SHR-SP and normotensive Wistar Kyoto rats (WKY).
2 In unstimulated artery, hyperpolarization evoked by acotylcholine was not
different in WKY and in NaCl-loaded WKY; it was reduced in SHR-SP and furt
her reduced in NaCl-loaded SHR-SP. Hyperpolarization was unaffected by N-om
ega-nitro-L-arginine (L-NA) but was abolished in high-KCl solution.
3 In noradrenaline-stimulated artery, ACh-evoked hyperpolarization and rela
xation were not different in WKY and in SHR-SP. NaCl-treatment did not affe
ct the responses to ACh in WKY but decreased maximum relaxation in SHR-SP f
rom 93 +/- 2% to 72 +/- 7% of the contraction. In WKY, in NaCl-loaded WKY a
nd in SHR-SP, L-NA similarly shifted the concentration-relaxation curve to
ACh to the right and depressed its maximum but L-NA did not affect the hype
rpolarization to ACh. In NaCl-loaded SHR-SP, L-NA blunted the effects of AC
h on membrane potential and on contraction.
4 The NO donor SNAP abolished the depolarization and the contraction evoked
by noradrenaline with the same potency in WKY and in untreated SHR-SP but
was more potent in NaCl-loaded SHR-SP.
5 In KCl-contracted arteries the relaxations to ACh were not different in W
KY and SHR-SP but NaCl-loaded SHR-SP were more sensitive to ACh.
6 The results showed that NaCl-rich diet markedly reduced the L-NA-resistan
t responses to ACh and increased the sensitivity to NO in SHR-SP.