The role of gaseous mediators (CO, NO and H2S) in the regulation of blood circulation: analysis of the participation of blood cell microrheology

Among the signaling molecules involved in the regulation of intra- and intercellular systems in various types of cells, a special place is occupied by gaseous compounds – gasotransmitters (GTs). Currently, the most studied are three molecules: nitrogen oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). For them, the enzymatic systems of intracellular synthesis and degradation have been determined, the physiological effect has been proved, and the intracellular mechanisms have been determined. Changes in the work of these mechanisms under the influence of GTs causes the development of physiological and/or pathophysiological reactions. These GTs are involved in the regulation of various organs and systems of the human body under normal and pathological conditions, including the structure and function of the circulatory system. In this article, special attention is paid to the influence of all three GTs and their donors on the vascular and hemorheological aspect of the work of blood circulation, and especially on an underdeveloped problem – the microrheology of erythrocytes. It has been shown that all three GTs, along with the well-known vasodilating effect, reduce the adhesion and aggregation of platelets and leukocytes, as well as moderately stimulate the deformability of erythrocytes and strongly inhibit their aggregation. The performed analysis of the data indicates that, along with the specific signaling cascades for each GT, the use of a common signaling pathway associated with soluble guanylate cyclase and NO synthase was also revealed in microrheological responses. The intersection of signaling pathways triggered by NO, CO and H2S on common effectors, as well as their interaction with each other (cross-talk), can determine the final, resulting functional response of the cell.

Hypotensive Effect Of The Plant Alkaloid Digitaalisen On The Functional Activity Of Mmc Aortic Chrysallida Of Dihydroemetine On The Functional Activity Of Smc In The Aorta Of The Rat

Effect of dihydroatizin (5–250 μmol / L) on the contractile activity of rat smooth aorta muscle cells (SMC). Isometric tensile forces were recorded. Using a force transducer FT - 03 (Grass Instrument Co., USA). In it was found by experiments that the vasodilating effect of dihydroatizin mainly associated with the blockade of the Ca2 + L-channel. Methods-Preparation of the aortic vessel muscle preparation, and recording the force of contraction. Results- KCI-induced contraction of the aortic MMC is associated with the activation of potential–dependent Ca2+L channels of the plasma membranes of the MMC Conclusions- The data obtained as a result of studying the mechanisms of action of the alkaloid dihydroathysine are of great practical importance and can be recommended for optimizing the process of purposeful creation of a new generation of vasorelaxant drugs

Penggunaan Calcium Channel Blocker pada Tatalaksana Anestesi Clipping Aneurisma Otak

Perdarahan subarachnoid dapat diartikan sebagai proses pecahnya pembuluh darah di ruang yang berada dibawah arakhnoid (subarachnoid). Prevalensi terjadinya perdarahan subaraknoid dapat mencapai hingga 33.000 orang per tahun di Amerika Serikat. Penyebab paling sering perdarahan subarachnoid adalah ruptur aneurisma salah satu arteri di dasar otak dan adanya malformasi arteriovena (MAV). Pada umumnya aneurisma terjadi pada sekitar 5% dari populasi orang dewasa, terutama pada wanita. Penanganan pada aneurisma pembuluh darah otak salah satunya dengan clipping aneurisma. Tindakan tersebut beresiko terjadi vasospasme serebral. Nimodipine adalah suatu calcium chanel blocker yang penting dalam pengelolaan operasi aneurisma karena mempunyai efek vasodilatasi pembuluh darah serebral dan termasuk dalam bagian dari manajemen vasospasme serebral. Pada laporan ini, dilaporkan dua kasus tindaan clipping aneurisma. Pasien pertama adalah wanita usia 69 tahun, berat badan 60 kg dengan diagnosa SAH hari ke 18 yang mengalami defisit neurologi berupa hemiparese dextra dan afasia motorik. Pasien kedua adalah wanita usia 57 tahun berat badan 60 kg dengan diagnosa SAH hari ke 20 dan mengalami defisit neurologi hemiparese kanan dan afasia sensorik. Pada kedua pasien dilakukan tindakan pembedahan kraniotomi clipping aneurisma. Kedua pasien memiliki hasil akhir yang baik. Akan tetapi, ada perbedaan lama perawatan antara pasien yang menjalani terapi awal nimodipine dan yang tidak menerima terapi tersebut.Administration of Calcium Channel Blocker in Anaesthesia Management of Cerebral Aneurysm ClippingAbstractSubarachnoid hemorrhage can be interpreted as the process of rupture of blood vessels in the space under the arachnoid (subarachnoid). The prevalence of subarachnoid hemorrhage can reach up to 33,000 people per year in the United States. The most common causes of subarachnoid bleeding are ruptured aneurysm in one of the arteries at the base of the brain and the presence of arteriovenous malformations (MAV). In general, aneurysms occur in about 5% of the adult population, especially in women.Therapy in cerebral vascular aneurysms, one of which is clipping aneurysms. These actions are at risk of cerebral vasospasm. Nimodipine is a calcium channel blocker which is important in the management of aneurysm surgery because it has a vasodilating effect on cerebral vessels and is included in the management of cerebral vasospasm. In this report, two cases of clipping aneurysm are reported. The first patient was a woman aged 69 years, body weight 60 kg with a diagnosis of SAH day 18 who had a neurological deficit in the form of hemiparese dextra and motor aphasia. The second patient was a 57-year-old woman weighing 60 kg with a diagnosis of SAH day 20 and had a neurological deficit in the form of right hemiparese and sensory aphasia. In both patients, clipping aneurysm was performed by craniotomy surgery. Both patients had good results. However, there is a difference in the length of stay between patients who underwent initial nimodipine therapy and who did not receive it.

Possible Mechanisms Involved in the Vasorelaxant Effect Produced by Anorexigenic Drugs in Rat Aortic Rings

Anorexigenics are compounds capable of reducing or suppressing appetite. Their three main types act on different neurotransmitters, either norepinephrine, serotonin or a combination of both. Among the drugs that act on norepinephrine are fenproporex, amfepramone and clobenzorex. Derivatives of the thyroid hormone triiodothyronine have also been associated with weight loss and used as a controversial treatment for obesity, despite their known cardiovascular side effects. Recent data suggest a possible vasodilating effect for these four substances that might be beneficial in a subset of patients. Herein we performed a systematic review of the literature (with emphasis on recent reports) to determine the implications and mechanisms of the vasodilating effects of some anorectics, specifically fenproporex, clobenzorex, amfepramone and triiodothyronine. Data analysis showed these four drugs to be vasodilating agents for rat aortic rings. The different mechanisms of action include endothelium-dependent vasodilation via activation of the NO-cGMP-PKG pathway and the opening of calcium-activated potassium channels. The finding of vasodilating activity indicates a potential role for some anorexigenic drugs in the treatment of obesity in hypertensive patients. Further in vivo studies are needed to test the clinical benefits of these four drugs.

Dl-3-N-butylphthalide attenuates ischemic reperfusion injury by improving the function of cerebral artery and circulation

Dl-3-N-butylphthalide (NBP) is approved in China for the treatment of ischemic stroke. Previous studies have shown that NBP promotes recovery after stroke via multiple mechanisms. However, the effect of NBP on vascular function and thrombosis remains unclear. Here, we aim to study the effect of NBP on vascular function using a rat model of transient middle cerebral artery occlusion (MCAO) and a state-of-the-art high-resolution synchrotron radiation angiography. Eighty SD rats underwent MCAO surgery. NBP (90 mg/kg) was administrated daily by gavage. Synchrotron radiation angiography was used to evaluate the cerebral vascular perfusion, vasoconstriction, and vasodilation in real-time. Neurological scores, brain infarction and atrophy were evaluated. Real-time PCR was used to assess the expression levels of thrombosis and vasoconstriction-related genes. Results revealed that NBP attenuated thrombosis after MCAO and reduced brain infarct and atrophy volume. NBP administrated at 1 and 4 h after MCAO prevented the vasoconstriction of the artery and maintained its diameter at normal level. Administrated at one week after surgery, NBP functioned as a vasodilator in rats after MCAO while displayed no vasodilating effect in sham group. Our results suggested that NBP attenuates brain injury via increasing the regional blood flow by reducing thrombosis and vasoconstriction.