Pradhan Ranjan K
Department of Biotechnology and School of Electrical Sciences, Odisha University of Technology and Research, Techno Campus, Ghatikia, Bhubaneswar, 751029 Odisha, India.
Comput Methods Programs Biomed. 2025 Jan;258:108495. doi: 10.1016/j.cmpb.2024.108495. Epub 2024 Nov 6.
Vasoconstriction of the resistance artery is mainly determined by an integrated action of multiple local stimuli acting on the vascular smooth muscle cells, which include neuronal delivery of α-adrenoceptor agonists and intraluminal pressure. The contractile activity of the arterial wall has been extensively studied ex vivo using isolated arterial preparations and myography techniques. However, agonist-mediated vasoconstriction response is often confounded by local effects of other stimuli (e.g., pressure) and, it remained unclear whether the pressure-induced myogenic response has any implication on the efficacy of agonist-mediated vasoconstriction during blood flow regulation in tissues. A quantitative understanding of the influence of each stimulus is necessary to understand the interaction between multiple regulatory mechanisms, which is required to ensure timely oxygen delivery to meet tissue needs.
We developed a simple empirical model of isolated vessel vasoreactivity that includes passive vessel wall mechanics and a lumped representation of active smooth muscle activation as a function of agonist concentration and pressure. Pressure myograph data in dog renal arterioles and rat femoral arterioles, isovolumic myograph data in rat femoral arteries, and vasoactive data in rat skeletal muscle arterioles were analyzed using the model. The effect of physiological pressure changes on the sensitivities of vascular segments to adrenergic agonists phenylephrine and norepinephrine was evaluated.
Model-based analysis of isolated vasoreactivity data, obtained due to changes in pressure and vasoconstricting agonists revealed that the strength of myogenic response of a resistance vessel has a strong influence on the sensitivity and dynamics of agonist response. An increase in intraluminal pressure was found to reduce the magnitude of agonist-mediated tone by lowering the sensitivity of the vessel segment to agonist. The passive mechanical properties of arterial wall considearably influence the agonist-mediated contraction in isolated arteries. These results demonstrate how passive vessel wall mechanics may dominate the vasoactive responses of the common myogenic and adrenergic pathways of smooth muscle contraction in blood flow regulation, supporting a long standing notion that there exists segment-specific vasoregulation in microvascular networks of various tissues.
The present model provides a simple and powerful tool for quantifying ex vivo vasoreactivity of asolated arteries to qualitatively study the interaction between myogenic and α-adrenergic control of vascular tone in isolated vessels. Analysis of pressure myography data and isovolumic myography data in different sizes of vessels and tissues, in response to norepinephrine and phenylephrine revealed the importance of passive vessel mechanics in arteriolar vasomotion and setting up of basal vasomotor tone at single vessel-level. The present study will be useful to quantify the extent to which myogenic tone may influence agonist-mediated vasoconstriction and agonist effect on pressure-mediated myogenic response in microvascular networks during blood flow regulation in tissues.
阻力动脉的血管收缩主要由作用于血管平滑肌细胞的多种局部刺激的综合作用决定，这些刺激包括神经元释放的α - 肾上腺素能激动剂和管腔内压力。动脉壁的收缩活性已通过离体动脉标本和肌动描记术进行了广泛的体外研究。然而，激动剂介导的血管收缩反应常常受到其他刺激（如压力）的局部效应的干扰，并且在组织血流调节过程中，压力诱导的肌源性反应对激动剂介导的血管收缩效能是否有影响仍不清楚。定量了解每种刺激的影响对于理解多种调节机制之间的相互作用是必要的，而这对于确保及时输送氧气以满足组织需求是必需的。
我们建立了一个简单的离体血管反应性经验模型，该模型包括被动血管壁力学以及作为激动剂浓度和压力函数的活性平滑肌激活的集总表示。使用该模型分析了犬肾小动脉和大鼠股小动脉的压力肌动描记数据、大鼠股动脉的等容肌动描记数据以及大鼠骨骼肌小动脉的血管活性数据。评估了生理压力变化对血管段对肾上腺素能激动剂去氧肾上腺素和去甲肾上腺素敏感性的影响。
基于模型对因压力和血管收缩激动剂变化而获得的离体血管反应性数据进行分析，结果显示阻力血管的肌源性反应强度对激动剂反应的敏感性和动力学有很大影响。发现管腔内压力升高会通过降低血管段对激动剂的敏感性来降低激动剂介导的张力幅度。动脉壁的被动力学特性在很大程度上影响离体动脉中激动剂介导的收缩。这些结果表明被动血管壁力学在血流调节中如何可能主导平滑肌收缩的常见肌源性和肾上腺素能途径的血管活性反应，支持了一个长期存在的观点，即各种组织的微血管网络中存在节段特异性血管调节。
本模型提供了一个简单而强大的工具，用于定量离体动脉的血管反应性，以定性研究离体血管中肌源性和α - 肾上腺素能对血管张力控制之间的相互作用。对不同大小血管和组织中对去甲肾上腺素和去氧肾上腺素的压力肌动描记数据和等容肌动描记数据的分析揭示了被动血管力学在小动脉血管运动和单血管水平基础血管运动张力建立中的重要性。本研究将有助于量化在组织血流调节过程中肌源性张力可能影响激动剂介导的血管收缩以及激动剂对微血管网络中压力介导的肌源性反应的影响程度。
