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It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.

Aim: The aim of our study was to clarify the cardioprotection of chronic intermittent hypobaric hypoxia (CIHH) and the underlying mechanism in spontaneously hypertensive rats (SHR)., Main Methods: Adult male rats were divided into normal blood pressure Wistar-Kyoto rats (WKY) control (WKY-CON), WKY rats with CIHH treatment (WKY-CIHH), SHR control (SHR-CON) and SHR with CIHH treatment (SHR-CIHH) groups. SHR-CIHH and WKY-CIHH rats were subjected to hypobaric hypoxia simulating 4000-m altitude for 35 days, 5 h per day. Arterial blood pressure and cardiac function parameters, including ejection fraction, fractional shortening and left ventricular (LV) wall thickness, were evaluated. Cardiac pathomorphology and myocardial fibrosis were determined. The expression of angiotensin-converting enzyme (ACE), ACE2, Ang II, Ang1-7, AT1 receptor, Mas receptor, IL-6, TNF-α，IL-10, SOD and MDA were assayed in myocardium., Key Findings: CIHH significantly decreased arterial blood pressure, alleviated LV hypertrophy, and improved cardiovascular function in SHR (P < 0.05-0.01). Also, CIHH protected SHR heart against morphological changes and fibrosis. In addition, CIHH significantly down-regulated the ACE/Ang II/AT1 receptor axis and up-regulated the ACE2/Ang1-7/Mas axis of renin-angiotensin system (RAS) in SHR (P < 0.05-0.01). CIHH significantly reduced IL-6, TNF-α, and MDA levels, but increased IL-10 and SOD in SHR myocardium (P < 0.05-0.01)., Significance: The CIHH treatment protected the heart of SHR against LV remodelling and myocardial fibrosis, which might be carried out through a balance in the ACE/Ang II/AT1 axis and the ACE2/Ang1-7/Mas axis of the RAS to reduce inflammation, and inhibit oxidative stress., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Endothelial damages are one of the most important causes of persistent hypertensive complications. The aim of our study was to discuss the relationship between the molecular markers of endothelial damage, thrombomodulin, and complications in hypertension., Methods: A total 132 cases of hypertensive patients, including 13 patients with damage of target organs, were selected as research subjects. And grouping was based on different levels of blood pressure. The blood pressure and thrombomodulin levels were detected among all cases, and their drinking, smoking, and other medical records were tracked., Results: Higher plasma concentration of thrombomodulin was demonstrated in subjects with hypertensive complications compared with without complications [24.5 (18.1,37.55) vs 12.1 (9.1,22.3) TU/mL, P = .001, respectively]. The optimum thrombomodulin cutoff value was determined to be more than 15.5 TU/mL, with a sensitivity of 92.3% and a specificity of 63%. With the increase in blood pressure level, thrombomodulin levels in three groups gradually raised [6.15(5.475,12.75) vs 9.75(7.725,13.35) vs 16.45 (10.125,23.725) TU/mL, P = .007, respectively]., Conclusion: With the increase in blood pressure and the occurrence of complications, thrombomodulin showed an increasing trend, which was caused by an increase in the degree of endothelial injury. So, thrombomodulin may serve as a clinically meaningful marker of the progression of hypertension., (© 2018 Wiley Periodicals, Inc.)

Elevation of blood pressure (BP) and blood viscosity (BV) was induced in unanesthetized Wistar rats by fixing and hanging. Electroacupuncture of "Zusanli" acupoint or microinjection of GABA (60 micrograms/10 microliters) into the IV ventricle of the brain could lower the high BP and BV induced by fixed-hanging, which could be blocked by a microinjection of GABAA receptor antagonist bicuculline (60 micrograms/10 microliters). The results showed that the depressant effect of electroacupuncture of "Zusanli" acupoint on high BP and blood hyperviscosity induced by fixed-hanging might be mediated by the activation of GABAA receptors in the brain.