Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats

Eur J Pharmacol. 2002 Mar 8;438(3):153-8. doi: 10.1016/s0014-2999(02)01311-0.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Amides / pharmacology
  • Animals
  • Basilar Artery / drug effects
  • Basilar Artery / physiology
  • Body Weight / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Cerebral Arteries / drug effects*
  • Cerebral Arteries / physiology
  • Dihydropyridines / pharmacology*
  • Dose-Response Relationship, Drug
  • Hypertension / physiopathology*
  • Male
  • Muscle Relaxants, Central / pharmacology
  • Nitric Oxide Donors / pharmacology
  • Nitroprusside / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Time Factors
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology

Substances

  • Amides
  • Calcium Channel Blockers
  • Dihydropyridines
  • Muscle Relaxants, Central
  • Nitric Oxide Donors
  • Pyridines
  • Vasodilator Agents
  • Y 27632
  • Nitroprusside
  • benidipine
  • Acetylcholine