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Altered cerebrovascular response to a potassium channel opener in hypertensive rats
H Takaba1, T Nagao, S Ibayashi
1Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Insights
Y-26763, an ATP-sensitive potassium channel opener, enhances cerebral blood flow in rats. This effect is reduced in hypertensive rats but restored by cilazapril, an ACE inhibitor, suggesting a preventative role for antihypertensive treatment.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Pharmacology
Background:
- ATP-sensitive potassium channels play a role in regulating cerebral blood flow.
- Hypertension can alter cerebrovascular responses to pharmacological agents.
Purpose of the Study:
- To investigate the effect of Y-26763, an ATP-sensitive potassium channel opener, on cerebral blood flow in stroke-prone spontaneously hypertensive rats (SHRSP).
- To determine if long-term antihypertensive treatment with cilazapril prevents alterations in cerebral blood flow response to Y-26763 in SHRSP.
Main Methods:
- Cerebral blood flow was measured during intracarotid infusion of Y-26763 in anesthetized SHRSP and Wistar-Kyoto rats (WKY).
- The effect of glibenclamide, a selective ATP-sensitive potassium channel inhibitor, was assessed.
- SHRSP underwent long-term antihypertensive treatment with cilazapril.
Main Results:
- Y-26763 dose-dependently increased cerebral blood flow in WKY, an effect inhibited by glibenclamide.
- The Y-26763-induced increase in cerebral blood flow was significantly impaired in SHRSP compared to WKY.
- Cilazapril treatment normalized blood pressure in SHRSP and prevented the impaired response to Y-26763.
Conclusions:
- ATP-sensitive potassium channels are involved in regulating rat cerebral blood flow.
- Hypertension diminishes the cerebrovascular response to ATP-sensitive potassium channel openers.
- Long-term antihypertensive treatment can prevent the altered cerebral blood flow response associated with chronic hypertension.
Abstract:
We examined whether the effect of Y-26763, an ATP-sensitive potassium channel opener, on cerebral blood flow is altered in stroke-prone spontaneously hypertensive rats (SHRSP) and, if altered, whether long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor, is capable of preventing the change. Cerebral blood flow during intracarotid infusion of Y-26763 was measured in anesthetized SHRSP and normotensive Wistar-Kyoto rats (WKY) as control. Y-26763 increased cerebral blood flow in a dose-dependent manner in WKY, and glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, inhibited the Y-26763-induced increase in cerebral blood flow. In contrast, the response to Y-26763 in SHRSP was significantly impaired compared with that in WKY. Antihypertensive treatment with cilazapril lowered blood pressure toward normal and prevented the impaired response in cerebral blood flow to Y-26763 in SHRSP. These findings suggest that (1) ATP-sensitive potassium channels contribute to the regulation of cerebral blood flow in rats, (2) the response to an ATP-sensitive potassium channel opener is markedly diminished in hypertensive rats, and (3) the altered response to an ATP-sensitive potassium channel opener during chronic hypertension can be prevented by long-term antihypertensive treatment.