Biology subjects

Mustafa, M. R.

Publications and source records attributed to Mustafa, M. R..

2 recordsLinked to original sources

bioRxiv2025

The impact of testosterone on paraventricular nucleus gene expression in male and female spontaneously hypertensive rats

BackgroundHypertension is a polygenic, complex disease that impacts men and women differently; whilst the incidence of high blood pressure (BP) is roughly equal over a lifetime, men typically are at higher risk of developing the disease earlier in life, before 50 years of age. There is adequate evidence that the brain is critical for the BP setpoint. The paraventricular nucleus (PVN) of the hypothalamus is an integrative structure that can influence not only neurohumoral responses to blood pressure changes, but also sympathetic drive. Here we manipulate the androgenic status of both male and female spontaneously hypertensive rats (SHRs) to determine how this changes gene expression within the PVN of these animals. MethodsSHR (8-weeks old) were either sham-operated or orchiectomized, whereas all females were oophorectomized, half of which received 10mg testosterone propionate subcutaneously. Mean arterial pressure (MAP) and testosterone (T) were measured by carotid cannulation and ELISA respectively. Sequencing was performed on hand-punched PVN sections and subjected to robust bioinformatic analysis. ResultsIn total, 6,571 differentially regulated genes (DRGs) are regulated in the PVN of male and female rats. High T (endogenous or replaced) correlates with higher MAP in both sexes. Orchidectomy-induced T depletion resulted in the significant regulation of 5,104 genes, involved in thousands of biological roles, including ones related to hormone and sex-hormone signalling. In the female SHR, testosterone replacement in oophorectomized animals induced the regulation of 1,727 genes, sharing many biological functions with those in the high T males. We validated key genes by qPCR to determine false discovery rate. ConclusionsT status in hypertensive rats correlates with MAP, and consistent changes in PVN transcriptome

neuroscience↗

bioRxiv2019

Effect of high-salt diet on mean arterial pressure, renal epithelial sodium channels and aquaporins subunits expression levels in Spontaneously Hypertensive Rats

An increase in blood pressure (BP) by a high-salt (HS) diet may involve the changes in the expression of epithelium sodium channels (ENaCs) and aquaporins (AQPs) in the kidney which affect the sodium- and water-handling mechanisms. In the present study, spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were exposed to HS and regular-salt (RS) diets for 6 weeks and fluid intake was monitored. After 6 weeks, mean arterial pressure (MAP) and plasma hormonal activity of atrial natriuretic peptide (ANP), levels of angiotensin II (Ang II), aldosterone and arginine vasopressin (AVP) were determined. The expression of mRNA and protein levels of ENaC and AQP subunits in kidneys were quantified by real-time PCR and Western blotting. High-salt diet caused higher MAP only in SHRs and higher fluid intake in both strains of rats when compared with their respective controls on RS diet. The plasma levels of Ang II and aldosterone were low in both SHRs and WKY rats fed with HS diet. Meanwhile, plasma ANP activity was high in both strains of rats on HS diet; whilst the AVP showed vice versa effects. The renal expression of mRNA and protein levels of - and {gamma}-ENaCs was lowered by HS diet in both SHRs and WKY rats. Although {beta}-ENaC mRNA and protein expression levels were depressed in SHRs but they were enhanced in WKY rats. On the other hand, AQP-1, 2 and 7 mRNA and protein expression levels were lowered in both strains of rats fed with HS diet, while that of AQP-3, 4 and 6 showed no significant changes. The suppression of mRNA and protein expression levels of ENaC and AQP subunits suggests that the HS-induced increase in the MAP of SHRs may not be due to the renal sodium and water retention solely.

physiology↗