Ang II Upregulation of the T-Lymphocyte Renin-Angiotensin System Is Amplified by Low-Grade Inflammation in Human Hypertension

BACKGROUND Low-grade inflammation facilitates the development of essential hypertension and target organ damage (TOD). Recently, human T-lymphocytes were shown to be endowed with a functional active renin-angiotensin system (RAS). We investigated whether in hypertensive patients a selective angiotensin (Ang) II-driven upregulation of T-cell RAS occurs and whether it is differently modulated in presence of low-grade inflammation. METHODS T-lymphocytes were obtained from 21 hypertensives (I-II World Health Organization class; 16 males, 5 females; 56 11 years). Low-grade inflammation was defined for high sensitive C-reactive protein (hsCRP) >2 mg/l.Ten healthy subjects formed the age- and sex-matched control group. After T-lymphocytes isolation, mRNAs for angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1-R) were quantified by reverse-transcriptase PCR with or without 0.1 pmol/l Ang II in addition to T-cells cultures. Cell pellet and supernatant ACE activity and Ang II content were measured. Cardiac and renal TOD-indexes were evaluated. RESULTS Both in controls and hypertensives, Ang II-stimulation significantly increased ACE and AT1-R mRNA levels (P < 0.05). In patients, the increase was earlier and higher than controls, with the highest values in hypertensives with >2 mg/l hsCRP. Peak Ang II-induced ACE and AT1-R mRNA levels were positively related to hsCRP, systolic blood pressure and body mass index (BMI) at the univariate analyses.The stepwise regression analyses selected hsCRP (r = 0.47) and left ventricular mass index (LVMI) (r = 0.50) as the variables independently related to peak ACE-gene expression, while BMI resulted independently related to peak AT1-R gene expression (P < 0.001). CONCLUSIONS In hypertension, an Ang II-driven activation of T-cell RAS, further amplified by low-grade inflammation, does occur and is associated to worse TOD. New therapeutic approaches aimed at this specific target might be proposed to control hypertension and hypertensive damage.