塞利洛尔对Wistar-Kyoto大鼠和自发性高血压大鼠心血管质量及心室功能的影响

Horinaka S, Frohlich E D

Alton Ochsner Medical Foundation, New Orleans, LA 70121.

Cardiovasc Res. 1992 Apr;26(4):396-400. doi: 10.1093/cvr/26.4.396.

OBJECTIVE

The effects of a new beta 1 adrenergic receptor blocking agent with beta 2 receptor agonistic properties on cardiovascular mass, left ventricular function, and aortic distensibility were studied in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats.

METHODS

20 male SHR and 20 male WKY rats (10 treated and 10 untreated) aged 22 weeks were studied after three weeks of treatment. Cardiovascular mass was measured and left ventricular function was assessed using electromagnetic flowmetry while rapidly infusing whole blood at pharmacologically reduced mean arterial pressure and at pretreatment arterial pressure levels. Aortic distensibility was assessed by obtaining pressure-volume relationships in isolated aortic segments.

RESULTS

Mean arterial pressure was reduced without changing cardiac output in SHR (p less than 0.01); it remained unchanged in WKY despite reduced cardiac output. Most noteworthy, and like no other agent studied to date, celiprolol significantly reduced both left and right ventricular as well as aortic mass in both WKY and SHR. Despite these similar mass reductions, celiprolol improved left ventricular function (p less than 0.01) and aortic distensibility (p less than 0.05) only in the SHR, a function maintained even when mean arterial pressure was increased abruptly to pretreatment levels.

CONCLUSIONS

Unlike other beta receptor blockers (or any other agent studied in the SHR), celiprolol was effective in reducing mass of right and left ventricles and of aorta; decreasing mean arterial pressure through a fall in total peripheral resistance; and improving left ventricular function and aortic distensibility in the SHR. In contrast, while these structural changes were also produced in WKY, they were not associated with similar functional responses. These findings provide further support for the thesis of a structural and haemodynamic dissociation in antihypertensive therapy.

目的

在Wistar-Kyoto（WKY）大鼠和自发性高血压（SHR）大鼠中研究一种具有β2受体激动特性的新型β1肾上腺素能受体阻断剂对心血管质量、左心室功能和主动脉扩张性的影响。

方法

对20只22周龄的雄性SHR大鼠和20只雄性WKY大鼠（10只接受治疗，10只未治疗）进行为期三周的治疗后进行研究。测量心血管质量，并在以药理学方法降低平均动脉压和预处理动脉压水平时，通过电磁血流仪评估左心室功能，同时快速输注全血。通过获取离体主动脉节段的压力-容积关系来评估主动脉扩张性。

结果

SHR大鼠的平均动脉压降低，而心输出量未改变（p<0.01）；WKY大鼠的心输出量降低，但其平均动脉压保持不变。最值得注意的是，与迄今为止研究的其他药物不同，塞利洛尔显著降低了WKY大鼠和SHR大鼠的左、右心室以及主动脉质量。尽管有这些相似的质量降低，但塞利洛尔仅在SHR大鼠中改善了左心室功能（p<0.01）和主动脉扩张性（p<0.05），即使平均动脉压突然升高至预处理水平，该功能仍得以维持。

结论

与其他β受体阻滞剂（或在SHR大鼠中研究的任何其他药物）不同，塞利洛尔可有效降低右心室、左心室和主动脉的质量；通过降低总外周阻力来降低平均动脉压；并改善SHR大鼠的左心室功能和主动脉扩张性。相比之下，虽然WKY大鼠也出现了这些结构变化，但它们并未伴有类似的功能反应。这些发现为抗高血压治疗中结构与血流动力学分离的论点提供了进一步支持。