Several signalling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction and variations in the renin-angiotensin-aldosterone system (RAAS). miRNAs comprise a family of small non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. miRNAs are involved in the development of both cardiovascular damage and hypertension.
In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h<sup>-1</sup>) were included; 28.4% had hypertension.
Hence, neural control of blood pressure is mediated by a signaling network between leptin, TNFα, melanocortin, and glutamate and changes in dynamics due to central excess leptin and TNFα mediate the switch from normal physiology to obesity-related hypertension.
There is now convincing evidence from animal studies that major signals such as leptin and insulin have a sympathoexcitatory action in the hypothalamus to cause hypertension.
Finally, it might be postulated that alterations of mitochondrial dynamics in white adipose tissue could contribute to the development and maintenance of hypertension in obesity situations through leptin overproduction.
VPA administration prevented the progression of hypertension and inhibited the increase in expression of HDAC1 and RAS components.VPA did not affect plasma leptin level.
These observations suggested that COX-2 may have an important role in the effects of leptin on inflammation, such as the low-inflammatory disease hypertension.
In this model, neonatal leptin supplementation restores the physiologic leptin surge, attenuates the leptin-triggered sympathetic activation in adulthood and prevents leptin- or stress-evoked hypertension.
Hence, central leptin employs TNFα to mediate the diurnal blood pressure elevation in physiology while enhancement of this mechanism can contribute to hypertension development.
In this meta-analysis, we summarized the association of the II/I polymorphism in leptin gene and Gln223Arg polymorphism in LEPR gene with hypertension and circulating leptin.
Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity.
Many experimental and clinical studies have demonstrated that elevated leptin concentration in patients with obesity/metabolic syndrome contributes to the pathogenesis of cardiovascular disorders including arterial hypertension, atherosclerosis, restenosis after coronary angioplasty and myocardial hypertrophy.
Our results suggest that the Gln223Arg polymorphism of the leptin receptor is significantly associated with plasma leptin levels and left ventricular hypertrophy in hypertension.
The study confirmed that shorter alleles of microsatellites in the 3' flanking region of leptin are significantly associated with hypertension, however, the underlying mechanism remains unknown.
Furthermore, the Gln223Arg polymorphism was significantly associated with plasma leptin levels (p<0.001), while no correlations between Lys109Arg SNP and hypertension were found.
The major finding from the present study was that the natural rise in plasma leptin with weight-gain is insufficient to counterbalance high blood pressure associated with obesity, additional increases of circulating leptin levels with adenoviral leptin gene therapy led to normalisation of blood pressure in high-fat diet-induced obese and hypertensive rats.
Our results showing that higher blood pressure levels were found with the most prevalent -2548G>A genotype, whereas patients with the AA genotype seemed to be protected from hypertension, indicate that the -2548G>A polymorphism of LEP appears to be an important mediator of obesity hypertension.