Oxygen Transport
James N. Cobley, Gareth W. Davison in Oxidative Eustress in Exercise Physiology, 2022
Several redox processes have been reported to regulate microvascular blood flow and, consequently, influence oxygen transport to muscle (Trinity, Broxterman and Richardson, 2016; Costa et al., 2020; Kadlec and Gutterman, 2020). Blood flow induces shear stress on the endothelium, increasing the activity of NO• synthases (eNOS), which utilize oxygen and L-arginine to produce NO• and L-citrulline (Panday, Kar and Kavdia, 2021). Nitric oxide subsequently activates the soluble guanylate cyclase pathway in the vascular smooth muscle cells leading to vascular wall expansion and increased blood flow (Simmonds, Detterich and Connes, 2014) (Figure 4.6). In the same context, chronic supplementation with l-citrulline has been reported to increase NO• levels, peripheral blood flow, muscle oxygenation and exercise performance (Figueroa et al., 2017).
Clinical and Experimental Evaluation of Sympatho-Vagal Interaction: Power Spectral Analysis of Heart Rate and Arterial Pressure Variabilities
Irving H. Zucker, Joseph P. Gilmore in Reflex Control of the Circulation, 2020
Attempting some evaluation of this ongoing work, the HF component of heart rate variability appears as a widely accepted marker of vagal tone. In addition, we propose the LF component of arterial pressure variability as the primary marker of sympathetic tone. In fact, we note the following points: (i) The vascular smooth muscle is under a sympathetic regulation, while both parasympathetic and sympathetic activities influence the sinus-node rhythmical properties, (ii) There are circumstances such as various levels of physical exercise during which the LF pressure oscillations are increased from resting values (Furlan et al., 1987; Pagani et al., 1988a) even at a time when the total heart rate variability is drastically reduced (Baselli et al., 1987) and the LF component difficult to discern (Arai et al., 1989). (iii) While LF arterial pressure oscillations can clearly occur in absence of any heart rate variability, as proven by studies in patients with fixed-rate pacemakers (Pagani et al., work in progress), the inverse has not yet been observed, i.e., the presence of LF component in heart rate variability in absence of a similar component in arterial pressure variability.
REGULATORY MECHANISMS
David M. Gibson, Robert A. Harris in Metabolic Regulation in Mammals, 2001
endothelial cells, in response to the binding of acetylcholine to "muscarinic" plasma membrane receptors. In certain blood vessels acetylcholine causes relaxation of vascular smooth muscle cells which underlie the endothelial layer. NO is the link in this signal transmission by diffusing across cell boundaries from endothelial cells into adjacent smooth muscle cells. The intracellular NO sensor is a cytosolic enzyme guarnivi cyclase which synthesizes cyclic GMP to activate a cGMP-dcpcndcnt protein kinase (PKG). (Compare with ANT which binds to a plasma membrane receptor guanylyl cyclase, item one.) A PKG phosphorylation step dampens the myosin light chain kinase contractile system of smooth muscle. Opposing accumulation of cGMP is a cGMP-specific phosphodiesterase. Pharmaceutical agents have been developed that cause vascular dilation through the inhibition of this enzyme. The drug nitroglycerin is prescribed to clfcct prompt dilation of cardiac \asculaturc during episodes of anginal pain through the release ol NO in ■situ.
MiRNA: a potential target for gene diagnosis and treatment of atherosclerotic stroke
Published in International Journal of Neuroscience, 2021
Yi. Bao, Sijing. Li, Yayong. Ding, Xinyu. Du, Miao. Zhang, Wanjuan. Tang, Siqin. Zhou
In the aspect of vascular smooth muscle cells, K Knoepp et al. demonstrated that miRNA was involved in the differential gene regulation of vascular remodeling by inducing the formation of neointima through the femoral artery line bundle of C57BL/6 mice, which played a key role in the proliferation of vascular smooth muscle cells and provided a therapeutic target for in-stent restenosis after angioplasty [19]. Previous studies have found that miRNA-29, miRNA-143/145 and miRNA-221/222 are involved in the regulation of phenotypic transformation, proliferation and migration of vascular smooth muscle cells [20]. MiRNA-143/145 is expressed in many pathological and physiological processes and can control the smooth muscle cell phenotype. In the study of pluripotent mouse cardiac progenitor cells, miRNA-145 and miRNA-143 were found to be down-regulated in the injury or atherosclerotic vessels of smooth muscle cells with low proliferation and differentiation. KLF2 is a key regulator of endothelial gene expression patterns that induce atherosclerosis, and binding to the promoter induces a significant up-regulation of miRNA-143/145 clusters [21]. In addition, miRNA-145 and miRNA-143 synergistically target transcription factor networks, including kruppel-like factor 4, myocardin and Elk-1 (members of the ETS oncogene family), which promote the differentiation and proliferation of smooth muscle cells [22].
The vasorelaxant effect of Canarium odontophyllum Miq. (Dabai) extract in rat thoracic aorta
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Dayang Fredalina Basri, Nur Sa'adah Abdul Rahman, Shafreena Shaukat Ali, Satirah Zainalabidin
Vascular endothelium which is located between the circulating blood and vascular smooth muscle plays an important role in regulating the vascular tone. Modulation of vascular tone by endothelium is mediated by the release of vasodilators (NO and prostacyclin) and vasoconstrictors such as endothelin and angiotensin II [17]. Relaxation in vascular smooth muscle can occur through the NO/cGMP pathway. In endothelial cell, the calcium-calmodulin complex stimulates NO synthase (NOS), which later activates NO formation from L-Arginine. NO then enters the smooth muscle cells and stimulates guanylate cyclase, which increases intracellular cyclic guanosine monophosphate (cGMP). The increased of the intracellular cGMP then stimulate cGMP dependent protein kinases leading to a decrease in the calcium concentrations in the smooth muscle cells, which causes its relaxation [18].
Tadalafil for the treatment of benign prostatic hyperplasia
Published in Expert Opinion on Pharmacotherapy, 2019
Fabiola Zakia Mónica, Gilberto De Nucci
The disorders LUTS-BPH and ED present in older men and can also coexist as pathways in the bladder, prostate and corpus cavernosum are similar. Considering preclinical studies, tadalafil plays an important role in the pathophysiology of LUTS-BPH as it (i) relaxes vascular and non-vascular smooth muscle, (ii) increases tissues oxygenation, (iii) reduces afferent nerve activity, (iv) reduces bladder and prostate smooth muscle cell proliferation and (v) inflammation. Although the three PDE5 inhibitors sildenafil-Viagra, vardenafil-Levitra and tadalafil-Cialis approved by FDA share the same mechanism of action, the longer duration of action of tadalafil, its safety and tolerability makes it more advantageous than sildenafil and vardenafil and hence tadalafil is the only representative of PDE5 inhibitors approved to treating patients with LUTS secondary to BPH with or without ED. The enhanced prostate and bladder smooth muscle relaxation induced by long-term treatment with PDE5 inhibitors seen in animal models of bladder and prostate hypercontractility are translated into the clinic as patients with LUTS secondary to BPH with or without ED showed significant improvement on the IPSS, IPSS-Qol and IIEF-EF scores.
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