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高血压、衰老和降压治疗对阴部动脉形态的影响。

Impact of hypertension, aging, and antihypertensive treatment on the morphology of the pudendal artery.

机构信息

Department of Pharmacology & Toxicology, Queen's University, Kingston, Ontario, Canada.

出版信息

J Sex Med. 2011 Apr;8(4):1027-38. doi: 10.1111/j.1743-6109.2010.02191.x. Epub 2011 Feb 1.

Abstract

INTRODUCTION

Aging and hypertension increase the risk of erectile dysfunction (ED) and cardiovascular disease. Arterial insufficiency is likely a primary factor in hypertension-related ED. Given the dominance of internal pudendal arteries in controlling penile vascular resistance, pathological changes in this vessel would be critical for inducing ED in aged hypertensives.

AIM

We assessed the age-related impact of hypertension and its treatment on erectile function and pudendal artery structure in young and old spontaneously hypertensive rats (SHRs).

METHODS

Erectile responses were monitored in 15- and 77-week-old SHR and Wistar Kyoto (WKY) rats using apomorphine (80 mg/kg). At sacrifice, the vasculature was perfusion-fixed and aorta, renal, mesenteric, and internal pudendal arteries assessed morphometrically using light and electron microscopy. A separate group of 15-week SHR were treated with enalapril and hydrochlorothiazide (30 mg/kg/day, 2 weeks) followed by 2 weeks off treatment, after which the same vessels were assessed morphometrically. Arterial pressures were determined using radiotelemetry.

MAIN OUTCOMES MEASURED

Erectile function, vessel morphology (lumen diameter, wall thickness, cross-sectional area, extracellular matrix [ECM]) and arterial pressure.

RESULTS

Erectile responses were similar in young SHR and WKY (1.7 ± 0.80 vs. 1.4 ± 0.85) but declined significantly in aged SHR (0.3 ± 0.49). Vascular aging in SHR was associated with striking pudendal remodeling, characterized by marked neointimal proliferation and disruptions of the internal elastic lamina. This remodeling involved thickening of the medial layer (35 ± 6.0 µm vs. 81 ± 3.5 µm, P < 0.01), decreased lumen diameter (282 ± 6.3 µm vs. 250 ± 12.4 µm, P < 0.05) and increased ECM (10 ± 2.0 µm² vs. 26 ± 10.6 µm², P < 0.001). In old pudendals, there were significantly more round synthetic smooth muscle cells bordering the intima and in the neointima. Antihypertensive treatment decreased the wall:lumen ratio in young SHR pudendal arteries (-17%).

CONCLUSIONS

Vascular aging in SHR with ED involved distinctive pathogenic remodeling in the internal pudendal artery. In young SHR, brief antihypertensive therapy was able to regress this abnormal morphology.

摘要

简介

衰老和高血压会增加勃起功能障碍(ED)和心血管疾病的风险。动脉功能不全可能是高血压相关 ED 的主要因素。鉴于内阴部动脉在控制阴茎血管阻力方面的主导地位,该血管的病理变化对于诱导老年高血压患者的 ED 至关重要。

目的

我们评估了高血压及其治疗对年轻和老年自发性高血压大鼠(SHR)的勃起功能和阴部动脉结构的年龄相关性影响。

方法

使用阿朴吗啡(80mg/kg)监测 15 周和 77 周龄 SHR 和 Wistar Kyoto(WKY)大鼠的勃起反应。在牺牲时,使用光镜和电子显微镜对血管进行灌注固定,并评估主动脉、肾、肠系膜和阴部内动脉的形态计量学。一组 15 周龄的 SHR 接受依那普利和氢氯噻嗪(30mg/kg/天,2 周)治疗,然后停药 2 周,之后对相同的血管进行形态计量学评估。使用无线电遥测法测定动脉压。

主要观察指标

勃起功能、血管形态(管腔直径、壁厚度、横截面积、细胞外基质 [ECM])和动脉压。

结果

年轻 SHR 和 WKY 的勃起反应相似(1.7±0.80 与 1.4±0.85),但老年 SHR 明显下降(0.3±0.49)。SHR 的血管老化与明显的阴部重塑有关,其特征是明显的内膜增生和内弹性膜的破坏。这种重塑包括中膜(35±6.0μm 与 81±3.5μm,P<0.01)、管腔直径(282±6.3μm 与 250±12.4μm,P<0.05)和 ECM(10±2.0μm² 与 26±10.6μm²,P<0.001)的增加。在老年阴部动脉中,内膜边界和内膜新生处有更多的圆形合成平滑肌细胞。降压治疗降低了年轻 SHR 阴部动脉的壁腔比(-17%)。

结论

伴有 ED 的 SHR 的血管老化涉及阴部内动脉的独特致病重塑。在年轻的 SHR 中,短暂的降压治疗能够使这种异常形态逆转。

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