Mátrai Máté, Hetthéssy Judit, Nádasy György L, Monos Emil, Székács Béla, Várbíró Szabolcs
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Faculty of Medicine, Budapest, Hungary.
Gend Med. 2012 Dec;9(6):548-56. doi: 10.1016/j.genm.2012.10.012.
It is well known that sex differences occur in both the pathogenesis and therapy of hypertension. A deeper understanding of the underlying processes may be helpful when planning a personalized therapeutic strategy.
In laboratory animal experiments, we studied the early mechanisms of vascular adaptation of the intramural small coronary arteries that play a fundamental role in the blood supply of the heart.
In our study, an osmotic minipump was implanted into 10 male and 10 female Sprague-Dawley rats. The pump remained in situ for 4 weeks, infusing a dose of 100 ng/kg/min angiotensin II acetate. Four weeks later, the animals were killed, and the intramural coronary arteries from the left coronary branch, which are fundamentally responsible for the blood supply of the heart, were prepared. The pharmacologic reactivity and biomechanical properties of the prepared segments were studied in a tissue bath.
The relative heart mass and vessel wall thickness were greater in females than males (0.387 [0.009] g/100 g vs 0.306 [0.006] g/100 g body weight; 41.9 [4.09] μm vs 33.45 [3.37] μm on 50 mm Hg). The vessel tone and vasoconstriction in response to thromboxane agonists were, however, significantly more pronounced in males. The extent of relaxation in response to bradykinin was also greater in females. Although we observed inward eutrophic remodeling in females, an increase in wall stress and elastic modulus dominated in males.
The early steps of angiotensin II-dependent hypertension evoked very different adaptation mechanisms in males and females.
众所周知，高血压的发病机制和治疗均存在性别差异。在制定个性化治疗策略时，深入了解其潜在机制可能会有所帮助。
在实验室动物实验中，我们研究了壁内小冠状动脉血管适应性的早期机制，这些小冠状动脉在心脏血液供应中起重要作用。
在我们的研究中，将渗透微型泵植入10只雄性和10只雌性Sprague-Dawley大鼠体内。泵原位放置4周，以100 ng/kg/min的剂量输注醋酸血管紧张素II。4周后，处死动物，制备来自左冠状动脉分支、对心脏血液供应起主要作用的壁内冠状动脉。在组织浴中研究制备节段的药理反应性和生物力学特性。
雌性大鼠的相对心脏质量和血管壁厚度大于雄性大鼠（0.387[0.009]g/100g体重vs0.306[0.006]g/100g体重；50mmHg时为41.9[4.09]μm vs33.45[3.37]μm）。然而，雄性大鼠对血栓素激动剂的血管张力和血管收缩明显更显著。雌性大鼠对缓激肽的舒张程度也更大。虽然我们在雌性大鼠中观察到内向性肥厚性重塑，但在雄性大鼠中壁应力和弹性模量增加占主导。
血管紧张素II依赖性高血压的早期阶段在雄性和雌性大鼠中引发了非常不同的适应机制。
