Characterization of Contractile Machinery of Vascular Smooth Muscles in Hypertension

Hypertension is a key risk factor for cardiovascular disease and it is a growing public health problem worldwide. The pathophysiological mechanisms of vascular smooth muscle (VSM) contraction contribute to the development of hypertension. Calcium (Ca2+)-dependent and -independent signaling mechanisms regulate the balance of the myosin light chain kinase and myosin light chain phosphatase to induce myosin phosphorylation, which activates VSM contraction to control blood pressure (BP). Here, we discuss the mechanism of the contractile machinery in VSM, especially RhoA/Rho kinase and PKC/CPI-17 of Ca2+ sensitization pathway in hypertension. The two signaling pathways affect BP in physiological and pathophysiological conditions and are highlighted in pulmonary, pregnancy, and salt-sensitive hypertension.

Molecular Mechanisms and Targets of Cyclic Guanosine Monophosphate (cGMP) in Vascular Smooth Muscles

Molecular mechanisms and targets of cyclic guanosine monophosphate (cGMP) accounting for vascular smooth muscles (VSM) contractility are reviewed. Mathematical models of five published mechanisms are presented, and four novel mechanisms are proposed. cGMP, which is primarily produced by the nitric oxide (NO) dependent soluble guanylate cyclase (sGC), activates cGMP-dependent protein kinase (PKG). The NO/cGMP/PKG signaling pathway targets are the mechanisms that regulate cytosolic calcium ([Ca2+]i) signaling and those implicated in the Ca2+-desensitization of the contractile apparatus. In addition to previous mathematical models of cGMP-mediated molecular mechanisms targeting [Ca2+]i regulation, such as large-conductance Ca2+-activated K+ channels (BKCa), Ca2+-dependent Cl− channels (ClCa), Na+/Ca2+ exchanger (NCX), Na+/K+/Cl− cotransport (NKCC), and Na+/K+-ATPase (NKA), other four novel mechanisms are proposed here based on the existing but perhaps overlooked experimental results. These are the effects of cGMP on the sarco−/endo- plasmic reticulum Ca2+-ATPase (SERCA), the plasma membrane Ca2+-ATPase (PMCA), the inositol 1,4,5-trisphosphate (IP3) receptor channels type 1 (IP3R1), and on the myosin light chain phosphatase (MLCP), which is implicated in the Ca2+-desensitization. Different modeling approaches are presented and discussed, and novel model descriptions are proposed.

ANALYSIS OF POLLUTION WITH NITROGEN OXIDES AIRSPACE TERRITORY KIEV

The article examines the level of pollution of the territory of the city of Kiev with nitrogen oxides, which is mainly formed by traffic flows on the main roads of the city. According to statistics, on average, one passenger car emits about one kilogram of various toxic and carcinogenic substances into the atmosphere per day. For the human body, nitrogen oxides are even more harmful than carbon monoxide. The general nature of the influence varies depending on the content of various nitrogen oxides: NO, NO2, N2O3, N2O4. Nitric oxide relaxes vascular smooth muscles, is involved in protection against pathogens, is a neurotransmitter, regulates programmed cell death and proliferation, and plays an important role in the secretory and reproductive system. Measurement of the concentration of nitrogen oxides for three days in the center of Kiev on the territory of the park named after Taras Grigorievich Shevchenko, which is surrounded by highways, showed the highest dynamics of changes in the content of the pollutant. The obtained results of calculating the pollution by nitrogen oxides near the main roads are almost ten times different from the data obtained by remote sensing (satellite) and measured at stationary stations, which indicates the excessive anthropogenic load of transport on the environment, especially in the center. Kiev and the need for additional control at points close to the main roads. When deciding on the placement of highways in the city plan, it is necessary to take into account the direction and speed of the wind. if the width of the roadside contamination with a pollutant crosses the border of the residential area, the value of the excess of the MPC standard in the air of the settlement at the calculated point on the border of the residential area should be calculated and protective measures should be provided.

Review of Chemical, Pharmacological, Biological Activities of Isatin and Its Derivatives – Part-2 (2002 To 2020)

: Isatin is a naturally occurring substance identified in humans, animals, plants and coal tar. Isatin derivatives are reported to possess a wide range of activites. This review is in continuation of “Part-1 (1877-2002)” review published by our team. This review encompasses the most signigicant reports published during 2002 to 2020 on the biological & pharmacological activites of isatin and its derivatives. The review includes the various synthetic reactions of isatin and activites reported. The pharmacological and biological activites reported were antimicrobial, antineoplastic & related activities; analgesic, anti-inflammatory, anticonvulsant, antioxidant, activity against veterinary pathogen, effects on cardiac & vascular smooth muscles; transthyretin fibrillogenesis inhibitor and antiglycation activity of isatin compounds.

Scar-modulating agents post urethroplasty: Could phosphodiesterase-5 inhibitors be the answer?

Background: Phosphodiesterase enzyme inhibitors (PDEIs) are most commonly prescribed by urologists for the treatment of erectile dysfunction. They are also gaining popularity as a treatment for lower urinary tract symptoms, based on their effect on smooth muscles – either vascular smooth muscles or smooth muscles in the urinary tract. For vascular smooth muscles, they cause vasodilation, enhanced microcirculatory haemodynamics through inhibition of platelet aggregation and adhesion, induction of apoptosis of adhesion fibroblasts and a reduction in the scarring process. Methodology: We reviewed articles published in English and indexed in the PubMed, Embase and Google Scholar databases, and consulted textbooks. Key search terms used were: urethral stricture, anti-fibrotic, scar-modulating agent, PDEIs, urethral scarring and urethroplasty. We created a synopsis of relevant articles, including original research studies and reviews. Level of evidence: Not applicable.