Le Roy A L, Messer-Létienne I, Bernard N, Benzoni D
Département de Physiologie et Pharmacologie Clinique, ESA CNRS 5014, Faculté de Pharmacie, Lyon, France.
J Cardiovasc Pharmacol. 1999 Jan;33(1):65-9. doi: 10.1097/00005344-199901000-00010.
This study aimed to evaluate the role of L-type calcium channels in the increased renal vascular resistance (RVR) of the Lyon hypertensive (LH) rat before and after normalization of its blood pressure (BP) by angiotensin-converting enzyme inhibition with perindopril. Concentration-response curves to Bay K 8644 (from 0.1 nM to 1 microM), a selective agonist of L-type calcium channels, were obtained in single-pass perfused kidneys isolated from groups of eight untreated or perindopril-treated (3 mg/kg/day, p.o., from age 3 to 7 weeks) LH and low-BP (LL) control rats. In untreated rats, the negative logarithm of the molar concentration of Bay K 8644 required to produce a half-maximal effect (pD2) values for Bay K 8644 did not differ between the two strains, whereas the maximal RVR response was higher in LH than in LL kidneys (28.0+/-4.9 vs. 12.9+/-0.8 mm Hg/ml/min/g, respectively). Perindopril normalized BP and RVR in LH rats and suppressed the interstrain differences in the maximal RVR responses (11.4+/-0.6 vs. 10.5+/-1.2 mm Hg/ml/min/g in LH and LL rats, respectively). These results demonstrate that LH rats exhibit an increased maximal contractile response to Bay K 8644 compared with LL controls, and that this alteration is not a primary defect because it disappears after normalization of BP level.
本研究旨在评估L型钙通道在利昂高血压（LH）大鼠经培哚普利抑制血管紧张素转换酶使血压（BP）正常化前后肾血管阻力（RVR）增加中所起的作用。在从8只未治疗或经培哚普利治疗（3mg/kg/天，口服，从3至7周龄）的LH和低血压（LL）对照大鼠组分离的单通道灌注肾脏中，获得了对L型钙通道的选择性激动剂Bay K 8644（浓度范围从0.1 nM至1μM）的浓度-反应曲线。在未治疗的大鼠中，两种品系产生半数最大效应所需的Bay K 8644摩尔浓度的负对数（pD2）值无差异，而LH肾脏的最大RVR反应高于LL肾脏（分别为28.0±4.9和12.9±0.8 mmHg/ml/min/g）。培哚普利使LH大鼠的血压和RVR正常化，并消除了最大RVR反应中的品系间差异（LH和LL大鼠分别为11.4±0.6和10.5±1.2 mmHg/ml/min/g）。这些结果表明，与LL对照相比，LH大鼠对Bay K 8644表现出更大的最大收缩反应，并且这种改变不是原发性缺陷，因为它在血压水平正常化后消失。
