Further Understanding about the Mechanism of Vitamin D on Blood Pressure

Globally, the prevalence of vitamin D deficiency and hypertension is both increasing. Various studies have also identified that both are likely to have causality relationships. The mechanisms and possibilities of such relationships will be discussed in this article. This literature study takes systematic review and meta-analysis research as well as randomly other research to complete the discussion on the role, effects, and mechanisms of vitamin D to blood pressure. Vitamin D is a fat-soluble vitamin that can be produced by the body and the most proper measurement using 25(OH)D. Low vitamin D is one of the risk factors for increased blood pressure (BP). Administration of vitamin D seems beneficial to lowering BP through various mechanisms including inhibit renin gene expression, maintain PTH levels and calcium homeostasis, vasodilatation BP, and decrease sympathetic nerve activity. Research with vitamin D supplementation reported random data between effective and whether or not to decrease BP. Vitamin D can be significantly beneficial in only some conditions although overall it has increased levels of 25(OH)D. However, although vitamin D is very good for health improvement, the use of vitamin D specifically as an antihypertensive still needs more understanding and research on the conditions that have proven effective in their use.

The Renin Cell Baroreceptor, A Nuclear Mechanotransducer Central for Homeostasis

Rationale: Renin-expressing cells are myoendocrine cells crucial for survival. They have been postulated to possess a pressure-sensing mechanism, a baroreceptor, that can detect slight changes in blood pressure and respond with precise and synchronized amounts of renin synthesized and released to the circulation to maintain blood pressure and fluid-electrolyte balance. The location and nature of this puzzling pressure-sensing structure have remained unknown since it was originally suggested over sixty years ago. Objective: To elucidate the location and structure of the renin cell baroreceptor. Methods and Results: We used a variety of genetically modified mice whereby renin cells were exposed in vivo to either low or high arterial pressure. In addition, we applied direct mechanical stimuli, i.e., pneumatic pressure or stretch, directly to renin cells cultured under different conditions and substrata. Changes in perfusion pressure and/or direct mechanical stimuli induced significant changes in renin gene expression and the phenotype of renin cells. Importantly, the experiments show that the pressure-sensing mechanism (the baroreceptor) resides in the renin cells; it requires initial extracellular sensing by integrin β1 at the renin cell membrane and is transduced to the nuclear membrane and chromatin by lamin A/C. Conclusions: These studies show that the enigmatic baroreceptor is a nuclear mechanotransducer that resides in the renin cells per se and is responsible for the sensing and transmission of extracellular physical forces directly to the chromatin of renin cells via lamin A/C to regulate renin gene expression, renin bioavailability, and homeostasis.

20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic rats

We hypothesized that vascular actions of 20-hydroxyeicosatetraenoic acid (20-HETE), the product of cytochrome P450 (CYP450)-dependent ω-hydroxylase, potentiate prohypertensive actions of angiotensin II (ANG II) in Cyp1a1-Ren-2 transgenic rats, a model of ANG II-dependent malignant hypertension. Therefore, we evaluated the antihypertensive effectiveness of 20-HETE receptor antagonist (AAA) in this model. Malignant hypertension was induced in Cyp1a1-Ren-2 transgenic rats by activation of the renin gene using indole-3-carbinol (I3C), a natural xenobiotic. Treatment with AAA was started either simultaneously with induction of hypertension or 10 days later, during established hypertension. Systolic blood pressure (SBP) was monitored by radiotelemetry, indices of renal and cardiac injury, and kidney ANG II levels were determined. In I3C-induced hypertensive rats, early AAA treatment reduced SBP elevation (to 161 ± 3 compared with 199 ± 3 mmHg in untreated I3C-induced rats), reduced albuminuria, glomerulosclerosis index, and cardiac hypertrophy (P<0.05 in all cases). Untreated I3C-induced rats showed augmented kidney ANG II (405 ± 14 compared with 52 ± 3 fmol/g in non-induced rats, P<0.05) which was markedly lowered by AAA treatment (72 ± 6 fmol/g). Remarkably, in TGR with established hypertension, AAA also decreased SBP (from 187 ± 4 to 158 ± 4 mmHg, P<0.05) and exhibited organoprotective effects in addition to marked suppression of kidney ANG II levels. In conclusion, 20-HETE antagonist attenuated the development and largely reversed the established ANG II-dependent malignant hypertension, likely via suppression of intrarenal ANG II levels. This suggests that intrarenal ANG II activation by 20-HETE is important in the pathophysiology of this hypertension form.