Paternò R, Faraci F M, Heistad D D
Department of Internal Medicine, University of Iowa College of Medicine (Iowa City) 52242-1081, USA.
Stroke. 1996 Sep;27(9):1603-7; discussion 1607-8. doi: 10.1161/01.str.27.9.1603.
The mechanisms by which cAMP and cGMP produce vasorelaxation are not entirely clear. In this study we examined the hypothesis that relaxation of cerebral arterioles in response to receptor-mediated activation of adenylate cyclase (increase in cAMP) is mediated through Ca(2+)-dependent K+ channels.
We measured the diameter of cerebral arterioles (basal diameter, 47 +/- 1 microns) using an open cranial window in anesthetized rats. Agonists and antagonists were applied locally in the cranial window.
Topical application of adenosine (0.1 and 1 mmol/L), a receptor-mediated activator of adenylate cyclase, and dibutyryl cAMP (60 and 200 mumol/L), a cell-permeable analogue of cAMP, dilated cerebral arterioles. Iberiotoxin (50 nmol/L), a selective inhibitor of Ca(2+)-dependent K+ channels, reduced vasodilatation in response to 0.1 and 1 mmol/L adenosine by 66% and 28%, respectively. Tetraethylammonium (TEA) (1 mmol/L), another inhibitor of Ca(2+)-dependent K+ channels, reduced vasodilatation to 0.1 and 1 mmol/L adenosine by 58% and 42%, respectively, and reduced vasodilatation in response to 60 and 200 mumol/L dibutyryl cAMP by 75% and 66%, respectively. Topical application of sodium nitroprusside (0.1 and 1 mumol/L), a direct activator of guanylate cyclase, and 8-bromo cGMP (200 and 600 mumol/L), a cell-permeable analogue, produced dilatation of cerebral arterioles that was inhibited by iberiotoxin (50 nmol/L) and TEA (1 and 3 mmol/L). In contrast, dilatation of cerebral arterioles in response to papaverine (which produces vasodilatation in large part by inhibition of Ca2+ channels) and aprikalim (which produces vasodilation by activation of ATP-sensitive K+ channels) was not inhibited by iberiotoxin or TEA.
These findings suggest that dilatation of cerebral arterioles by receptor-mediated activation of adenylate cyclase and by direct activation of guanylate cyclase in the rat is mediated in large part by activation of Ca(2+)-dependent K+ channels.
环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）产生血管舒张的机制尚不完全清楚。在本研究中，我们检验了以下假设：受体介导的腺苷酸环化酶激活（cAMP增加）所引起的脑动脉舒张是通过钙依赖性钾通道介导的。
我们在麻醉大鼠中使用开颅视窗测量脑动脉直径（基础直径为47±1微米）。激动剂和拮抗剂在颅窗局部应用。
局部应用腺苷（0.1和1 mmol/L），一种受体介导的腺苷酸环化酶激活剂，以及二丁酰环磷腺苷（60和200 μmol/L），一种可透过细胞的cAMP类似物，可使脑动脉舒张。埃博毒素（50 nmol/L），一种钙依赖性钾通道的选择性抑制剂，分别使对0.1和1 mmol/L腺苷的血管舒张减少66%和28%。四乙铵（TEA）（1 mmol/L），另一种钙依赖性钾通道抑制剂，分别使对0.1和1 mmol/L腺苷的血管舒张减少58%和42%，并分别使对60和200 μmol/L二丁酰环磷腺苷的血管舒张减少75%和66%。局部应用硝普钠（0.1和1 μmol/L），一种鸟苷酸环化酶的直接激活剂，以及8-溴环磷鸟苷（200和600 μmol/L），一种可透过细胞的类似物，可使脑动脉舒张，这种舒张被埃博毒素（50 nmol/L）和TEA（1和3 mmol/L）抑制。相比之下，对罂粟碱（其主要通过抑制钙通道产生血管舒张）和阿普卡林（其通过激活ATP敏感性钾通道产生血管舒张）的脑动脉舒张不受埃博毒素或TEA抑制。
这些发现表明，在大鼠中，受体介导的腺苷酸环化酶激活以及鸟苷酸环化酶的直接激活所引起的脑动脉舒张在很大程度上是由钙依赖性钾通道的激活介导的。
