Shahid Mohd, Buys Emmanuel S
Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School.
J Vis Exp. 2013 Jun 7(76):50328. doi: 10.3791/50328.
Pressure myograph systems are exquisitely useful in the functional assessment of small arteries, pressurized to a suitable transmural pressure. The near physiological condition achieved in pressure myography permits in-depth characterization of intrinsic responses to pharmacological and physiological stimuli, which can be extrapolated to the in vivo behavior of the vascular bed. Pressure myograph has several advantages over conventional wire myographs. For example, smaller resistance vessels can be studied at tightly controlled and physiologically relevant intraluminal pressures. Here, we study the ability of 3(rd) order mesenteric arteries (3-4 mm long), preconstricted with phenylephrine, to vaso-relax in response to acetylcholine. Mesenteric arteries are mounted on two cannulas connected to a pressurized and sealed system that is maintained at constant pressure of 60 mmHg. The lumen and outer diameter of the vessel are continuously recorded using a video camera, allowing real time quantification of the vasoconstriction and vasorelaxation in response to phenylephrine and acetylcholine, respectively. To demonstrate the applicability of pressure myography to study the etiology of cardiovascular disease, we assessed endothelium-dependent vascular function in a murine model of systemic hypertension. Mice deficient in the α1 subunit of soluble guanylate cyclase (sGCα1(-/-)) are hypertensive when on a 129S6 (S6) background (sGCα1(-/-S6)) but not when on a C57BL/6 (B6) background (sGCα1(-/-B6)). Using pressure myography, we demonstrate that sGCα1-deficiency results in impaired endothelium-dependent vasorelaxation. The vascular dysfunction is more pronounced in sGCα1(-/-S6) than in sGCα1(-/-B6) mice, likely contributing to the higher blood pressure in sGCα1(-/-S6) than in sGCα1(-/-B6) mice. Pressure myography is a relatively simple, but sensitive and mechanistically useful technique that can be used to assess the effect of various stimuli on vascular contraction and relaxation, thereby augmenting our insight into the mechanisms underlying cardiovascular disease.
压力肌动描记系统在小动脉的功能评估中极为有用，这些小动脉被加压至合适的跨壁压力。压力肌动描记法所实现的接近生理状态的条件使得能够深入表征对药理和生理刺激的内在反应，而这些反应可外推至血管床的体内行为。与传统的线式肌动描记法相比，压力肌动描记法有几个优点。例如，可以在严格控制且生理相关的腔内压力下研究较小的阻力血管。在此，我们研究用去氧肾上腺素预收缩的三级肠系膜动脉（长3 - 4毫米）对乙酰胆碱作出血管舒张反应的能力。将肠系膜动脉安装在连接到加压密封系统的两个插管上，该系统维持在60毫米汞柱的恒定压力。使用摄像机连续记录血管的管腔和外径，从而分别实时量化对去氧肾上腺素和乙酰胆碱的血管收缩和血管舒张。为了证明压力肌动描记法在研究心血管疾病病因方面的适用性，我们在系统性高血压小鼠模型中评估了内皮依赖性血管功能。在129S6（S6）背景下缺乏可溶性鸟苷酸环化酶α1亚基（sGCα1(-/-)）的小鼠是高血压（sGCα1(-/-S6)），但在C57BL/6（B6）背景下则不是（sGCα1(-/-B6)）。使用压力肌动描记法，我们证明sGCα1缺乏会导致内皮依赖性血管舒张受损。血管功能障碍在sGCα1(-/-S6)小鼠中比在sGCα1(-/-B6)小鼠中更明显，这可能是sGCα1(-/-S6)小鼠比sGCα1(-/-B6)小鼠血压更高的原因。压力肌动描记法是一种相对简单但灵敏且在机制上有用的技术，可用于评估各种刺激对血管收缩和舒张的影响，从而增强我们对心血管疾病潜在机制的理解。
