遗传性高血压中血管对Bay K 8644的反应性增加。

Increased vascular reactivity to Bay K 8644 in genetic hypertension.

作者信息

Bruner C A, Webb R C

机构信息

Department of Physiology, University of Michigan Medical School, Ann Arbor.

出版信息

Pharmacology. 1990;41(1):24-35. doi: 10.1159/000138696.

DOI:10.1159/000138696

PMID:1700445

Abstract

These experiments compared potential-operated calcium channel function in smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Carotid artery strips from adult male SHRSP and WKY rats were suspended in tissue baths for isometric force recording. Contractile force was expressed as percent of response to 100 mmol/l KCl. Vascular strips from SHRSP were more sensitive to KCl (ED50 = 25 mmol/l) compared to strips from WKY rats (ED50 = 37 mmol/l). The calcium channel agonist Bay K 8644 (2.8 x 10(-10) to 2.8 x 10(-7) mol/l) produced tonic contractions in carotid artery strips from SHRSP (34% of the contractile response to 100 mmol/l KCl) but not in those from WKY rats. Incubation of vascular strips in 1.8 or 6 x 10(-10) mmols/l norepinephrine did not alter the maximal contractile response to Bay K 8644 in either strain of rats. In 12 mmol/l KCl, the maximal contractile response to Bay K 8644 was increased in both SHRSP (71%) and WKY rats (25%). In 18 mmol/l KCl, maximal contractile responses to Bay K 8644 in the two strains were similar (SHRSP = 73%, WKY = 76%). Removal of the endothelium did not significantly affect contractile responses to Bay K 8644 in either strain of rats. There were no differences in contractile responses to the calcium ionophore A23187 or in nifedipine-induced relaxation of potassium-activated vessels between carotid arteries from SHRSP and WKY rats. In summary, these results suggest that a difference in voltage-operated calcium channel function may underlie the increased sensitivity of SHRSP vascular smooth muscle to depolarizing stimuli.

摘要

这些实验比较了易中风自发性高血压大鼠（SHRSP）和正常血压的Wistar-Kyoto大鼠（WKY）平滑肌中电压门控性钙通道的功能。将成年雄性SHRSP和WKY大鼠的颈动脉条悬挂于组织浴槽中进行等长张力记录。收缩力以对100 mmol/l KCl反应的百分比表示。与WKY大鼠的血管条（ED50 = 37 mmol/l）相比，SHRSP的血管条对KCl更敏感（ED50 = 25 mmol/l）。钙通道激动剂Bay K 8644（2.8×10⁻¹⁰至2.8×10⁻⁷ mol/l）在SHRSP的颈动脉条中产生强直收缩（为对100 mmol/l KCl收缩反应的34%），但在WKY大鼠的颈动脉条中未产生。将血管条置于1.8或6×10⁻¹⁰ mmol/l去甲肾上腺素中孵育，两种品系大鼠对Bay K 8644的最大收缩反应均未改变。在12 mmol/l KCl中，SHRSP（71%）和WKY大鼠（25%）对Bay K 8644的最大收缩反应均增加。在18 mmol/l KCl中，两种品系对Bay K 8644的最大收缩反应相似（SHRSP = 73%，WKY = 76%）。去除内皮对两种品系大鼠对Bay K 8644的收缩反应均无显著影响。SHRSP和WKY大鼠颈动脉对钙离子载体A23187的收缩反应或硝苯地平诱导的钾激活血管舒张反应均无差异。总之，这些结果表明电压门控性钙通道功能的差异可能是SHRSP血管平滑肌对去极化刺激敏感性增加的基础。