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Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats
Jiro Kitayama1, Takanari Kitazono, Hiroaki Ooboshi
1Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, 812-8582, Fukuoka, Japan.
Insights
Long-term use of benidipine, a calcium channel blocker, improved blood vessel function and reduced thickening in hypertensive rats. This suggests benidipine may protect cerebral arteries from hypertension-related damage.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Neuroscience
Background:
- Hypertension is associated with functional and morphological deterioration of cerebral arteries.
- Calcium channel blockers are widely used to manage hypertension.
- The specific effects of long-term calcium channel blocker treatment on cerebral artery function in hypertension require further investigation.
Purpose of the Study:
- To test the hypothesis that long-term application of a calcium channel blocker (benidipine) would ameliorate the functional and morphological deterioration of cerebral arteries during hypertension.
- To investigate the effects of benidipine on basilar artery responses to various vasodilators in spontaneously hypertensive rats (SHR).
Main Methods:
- Male spontaneously hypertensive rats (SHR) were treated with low or high doses of benidipine for 2 months.
- Cranial window technique was used to examine basilar artery responses to acetylcholine, sodium nitroprusside, Y-26763 (K+ channel opener), and Y-27632 (Rho-kinase inhibitor).
- Arterial pressure and basilar artery wall thickness were measured.
Main Results:
- Benidipine treatment significantly reduced mean arterial pressure in SHR.
- Dilator responses to acetylcholine and Y-26763 were impaired in SHR but enhanced by benidipine.
- Benidipine reduced the enhanced Y-27632-induced dilatation in SHR, suggesting reduced Rho-kinase activity.
- Benidipine treatment reduced basilar artery wall thickness in SHR.
- Nitroprusside-induced dilatation was unaffected by benidipine.
Conclusions:
- Chronic treatment with benidipine, a calcium channel blocker, enhances the dilator capacity of the basilar artery in hypertensive rats.
- Benidipine may ameliorate the morphological changes, such as wall thickening, of cerebral arteries during hypertension.
- These findings suggest a protective role for benidipine against hypertension-induced vascular damage in the brain.
Abstract:
We tested the hypothesis that long-term application of a Ca2+ channel blocker would ameliorate the functional and morphological deterioration of the cerebral arteries during hypertension. Male spontaneously hypertensive rats (SHR) were fed a standard rat chow, containing a low (3 mg/kg/day) or high dose (6 mg/kg/day) of benidipine, a Ca2+ channel blocker, for 2 months. Using a cranial window, we examined responses of the basilar artery to acetylcholine, sodium nitroprusside, (-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ol (Y-26763; an opener of ATP-sensitive K+ channels), and (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632; an inhibitor of Rho-associated kinase). Mean arterial pressure of the control group was 193+/-5 mm Hg (mean+/-S.E.M.), while that of the low-dose benidipine group was 183+/-5 mm Hg and that of the high-dose group was 159+/-4 mm Hg. Dilator responses of the basilar artery to acetylcholine and Y-26763 were impaired in SHR compared with those of normotensive Wistar-Kyoto (WKY) rats and treatment with benidipine enhanced the vasodilator responses to acetylcholine and Y-26763 in SHR. Y-27632-induced dilatation of the basilar artery was enhanced in SHR compared to that in WKY rats and the vasodilatation was reduced by benidipine in SHR. Sodium nitroprusside caused similar dilatation of the basilar artery, in both WKY rats and the SHR control group, and benidipine did not affect nitroprusside-induced dilatation of the artery in SHR. The wall of the basilar artery was significantly thicker in SHR than in WKY rats and benidipine treatment reduced the wall thickness of the artery in SHR. These findings suggest that chronic treatment with a Ca2+ channel blocker may enhance the dilator capacity and reduce contractility of the basilar artery during hypertension. Benidipine may also ameliorate the morphological changes of the basilar artery in hypertension.