scholarly journals Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4)

2021 ◽  
Vol 22 (18) ◽  
pp. 9925
Author(s):  
Natalie Längst ◽  
Julia Adler ◽  
Olga Schweigert ◽  
Felicia Kleusberg ◽  
Melanie Cruz Santos ◽  
...  

The cysteine-rich LIM-only protein 4 (CRP4), a LIM-domain and zinc finger containing adapter protein, has been implicated as a downstream effector of the second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) pathway in multiple cell types, including vascular smooth muscle cells (VSMCs). VSMCs and nitric oxide (NO)-induced cGMP signaling through cGMP-dependent protein kinase type I (cGKI) play fundamental roles in the physiological regulation of vascular tone and arterial blood pressure (BP). However, it remains unclear whether the vasorelaxant actions attributed to the NO/cGMP axis require CRP4. This study uses mice with a targeted deletion of the CRP4 gene (CRP4 KO) to elucidate whether cGMP-elevating agents, which are well known for their vasorelaxant properties, affect vessel tone, and thus, BP through CRP4. Cinaciguat, a NO- and heme-independent activator of the NO-sensitive (soluble) guanylyl cyclase (NO-GC) and NO-releasing agents, relaxed both CRP4-proficient and -deficient aortic ring segments pre-contracted with prostaglandin F2α. However, the magnitude of relaxation was slightly, but significantly, increased in vessels lacking CRP4. Accordingly, CRP4 KO mice presented with hypotonia at baseline, as well as a greater drop in systolic BP in response to the acute administration of cinaciguat, sodium nitroprusside, and carbachol. Mechanistically, loss of CRP4 in VSMCs reduced the Ca2+-sensitivity of the contractile apparatus, possibly involving regulatory proteins, such as myosin phosphatase targeting subunit 1 (MYPT1) and the regulatory light chain of myosin (RLC). In conclusion, the present findings confirm that the adapter protein CRP4 interacts with the NO-GC/cGMP/cGKI pathway in the vasculature. CRP4 seems to be part of a negative feedback loop that eventually fine-tunes the NO-GC/cGMP axis in VSMCs to increase myofilament Ca2+ desensitization and thereby the maximal vasorelaxant effects attained by (selected) cGMP-elevating agents.

2003 ◽  
Vol 284 (3) ◽  
pp. R628-R638 ◽  
Author(s):  
Pablo A. Ortiz ◽  
Jeffrey L. Garvin

Nitric oxide (NO) plays an essential role in the maintenance of cardiovascular and renal homeostasis. Endogenous NO is produced by three different NO synthase (NOS) isoforms: endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS). To investigate which NOS is responsible for NO production in different tissues, NOS knockout (−/−) mice have been generated for the three isoforms. This review focuses on the regulation of cardiovascular and renal function in relation to blood pressure homeostasis in the different NOS−/− mice. Although regulation of vascular tone and cardiac function in eNOS−/− has been extensively studied, far less is known about renal function in these mice. eNOS−/− mice are hypertensive, but the mechanism responsible for their high blood pressure is still not clear. Less is known about cardiovascular and renal control in nNOS−/− mice, probably because their blood pressure is normal. Recent data suggest that nNOS plays important roles in cardiac function, renal homeostasis, and regulation of vascular tone under certain conditions, but these are only now beginning to be studied. Inasmuch as iNOS is absent from the cardiovascular system under physiological conditions, it may become important to blood pressure regulation only during pathological conditions related to inflammatory processes. However, iNOS is constitutively expressed in the kidney, where its function is largely unknown. Overall, the study of NOS knockout mice has been very useful and produced many answers, but it has also raised new questions. The appearance of compensatory mechanisms suggests the importance of the different isoforms to specific processes, but it also complicates interpretation of the data. In addition, deletion of a single gene may have physiologically significant effects in addition to those being studied. Thus the presence or absence of a specific phenotype may not reflect the most important physiological function of the absent gene.


2021 ◽  
Author(s):  
Ewelina Zaorska ◽  
Marta Gawrys-Kopczynska ◽  
Ryszard Ostaszewski ◽  
Dominik Koszelewski ◽  
Marcin Ufnal

Methane is produced by carbohydrate fermentation in the gastrointestinal tract through the metabolism of methanogenic microbiota. Several lines of evidence suggest that methane exerts anti-inflammatory, anti-apoptotic and anti-oxidative effects. The effect of methane on cardiovascular system is obscure. The objective of the present study was to evaluate the hemodynamic response to methane. A vehicle or methane-rich saline were administered intravenously or intraperitoneally in normotensive anaesthetized rats. We have found no significant effect of the acute administration of methane-rich saline on arterial blood pressure and heart rate in anaesthetized rats. Our study suggests that methane does not influence the control of arterial blood pressure. However, further chronic studies may be needed to fully understand hemodynamic effects of the gas.


2020 ◽  
Vol 33 (4) ◽  
pp. 305-309
Author(s):  
Masashi Tawa ◽  
Takayoshi Masuoka ◽  
Yuka Yamashita ◽  
Katsuya Nakano ◽  
Takaharu Ishibashi

Abstract BACKGROUND Beetroot has attracted much attention because of its blood pressure-lowering properties. Although beetroot contains various nutritional compounds, including inorganic nitrate, some of their physiological properties are not fully understood. In this study, we examined whether betanin, a beetroot component, has a regulatory effect on vascular tone. METHODS Mechanical responses of isolated porcine coronary, mesenteric, and pulmonary arteries were assessed by organ chamber technique. In some cases, the vascular reactivity was observed in the presence of a physiological concentration of betanin (10 µM). RESULTS Betanin did not induce vasorelaxation at physiological concentrations both in endothelium-intact and -denuded coronary, mesenteric, and pulmonary arteries. The endothelium-dependent agonists, bradykinin and A23187 induced vasorelaxation of endothelium-intact coronary arteries, both of which were not affected by exposure to betanin. Likewise, endothelium-independent vasorelaxation induced by sodium nitrite and sodium nitroprusside was also not affected by the presence of betanin. In addition, exposure of endothelium-intact coronary arteries to betanin did not attenuate prostaglandin F2α- and endothelin-1-induced vasocontraction. CONCLUSIONS These findings suggest that betanin does not have a vasorelaxant activity. It is unlikely that betanin is a component directly responsible for the beetroot-induced acute blood pressure-lowering effect in a nitrate-independent manner.


Author(s):  
Matthias R. Meyer ◽  
Eric R. Prossnitz ◽  
Matthias Barton

2020 ◽  
Vol 65 (3) ◽  
Author(s):  
Ekaterina Podyacheva ◽  
Tatyana Zemlyanukhina ◽  
Lavrentij Shadrin ◽  
Tatyana Baranova

The adaptive cardiovascular reactions of the human diving reflex were studied. The diving reflex was activated by submerging a face in cold water under laboratory conditions. Forty volunteers (aged 18–24) were examined. ECG, arterial blood pressure (ABP) and central blood flow were recorded by the impedance rheography method in resting state, during diving simulation (DS) and after apnea. During DS there is a statistically significant decrease in the dicrotic index (DCI), which reflects a decrease in the resistive vessel tone and as well as diastolic index (DSI), characterizing lung perfusion. A comparison of the latent periods (LP) of an increase in ABP and a drop in DCI showed that a decrease in pulmonary vascular tone develops faster than ABP begins to increase. The LP for lowering DCI is from 0.6 to 10 s; for an increase in ABP — from 6 to 30 s. A short LP for DCI and the absence of a correlation between a decrease in ABP and DCI suggests that a decrease in pulmonary vascular tone during DS occurs reflexively and independently of a change in ABP.


Author(s):  
Виктория Киреева ◽  
Viktoriya Kireeva ◽  
Г. Лифшиц ◽  
G. Lifshic ◽  
Н. Кох ◽  
...  

Purpose of the study. To test the functional associations of polymorphic variants of genes in the regulation of blood pressure and vascular tone in employees of the ISC SB RAS. Materials and methods. The study involved patients, employees of the ISC SB RAS, being under care of the outpatient clinic of the Hospital of the ISC SB RAS. During routine laboratory testing the patients were taken 2 ml of blood for genetic analysis and further molecular genetic study on “Hypertension”, “Endothelial dysfunction”, “Pharmacogenetics”, “Inflammatory response” panels. Results. In the analysis of 12 genes coding for key proteins of hormonal enzyme blood pressure regulation systems, polymorphism of CYP11B2 showed statistically significant correlation with the presence of arterial hypertension, which makes its further study promising. The presence of allele C showed protective significance in relation to the development of hypertension with OR = 0,247. When checking associations of functional polymorphic variants of genes, the products of which are involved in the regulation of vascular tone, with hypertension in patients younger than 50 years old we found association of T/T rs5443GNB3 genotype with the debut of hypertensive disease under the age of 50. The data obtained allow the doctor to choose the most personalized and effective safe drug from certain groups, as well as its dose for employees having passed molecular genetic testing. These data can reveal predisposition to the most widespread and socially significant diseases in the surveyed subjects and provide specific personalized recommendations for the prevention of these diseases.


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