angiotensin-i and Essential-Hypertension

Primary aldosteronism is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio during screening process is a major confounder. Renin-angiotensin-aldosterone system Triple-A analysis is a novel liquid chromatography/tandem mass spectrometry diagnostic assay that allows simultaneous quantification of aldosterone, equilibrium Ang I (angiotensin I), and Equilibrium Ang II in a single sample of serum. We performed a comparative evaluation of the diagnostic performance of the aldosterone-to-Ang II ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the Ang II-to-Ang I ratio revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while aldosterone-to-Ang II ratio remained unaffected. The Youden index optimal cutoff value for the aldosterone-to-Ang II ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving noninferiority compared with the aldosterone-to-renin ratio while pointing to the potential for an interference-free application in patients under ACE (angiotensin-converting enzyme) inhibitor therapy. This study shows for the first time the accuracy and reliability of renin-angiotensin-aldosterone system triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.

Topics: Adult; Aldosterone; Angiotensin I; Angiotensin II; Essential Hypertension; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Renin-Angiotensin System; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

Angiotensin-converting enzyme 2 (ACE2) plays an important role in the development of essential hypertension (EH). Genetic factors remarkably influence circulating ACE2 level.. Because heritability had remarkable effects on circulating ACE2, we designed this study to shed light on whether circulating levels of ACE2, angiotensin-(1-7) and angiotensin-(1-9) were linked to single nucleotide polymorphisms (SNPs) and haplotypes in ACE2 gene.. A total of 213 patients with newly diagnosed mild to moderate EH were enrolled in the present study. Four ACE2 tag SNPs (rs2074192, rs4646171, rs4646155 and rs2106809) were genotyped, and major haplotypes consisting of these 4 SNPs were reconstructed for all subjects. Circulating levels of ACE2, angiotensin-(1-7) and angiotensin-(1-9) were measured using enzyme-linked immunosorbent assay.. In female subjects, linear regression analysis suggested that rare alleles of ACE2 rs2074192 and rs2106809 were associated with reduced circulating angiotensin-(1-7) levels (P=.007 and P=.006, respectively). ACE2 haplotype CAGC was associated with elevated circulating angiotensin-(1-7) levels (P=.03) whereas TAGT was associated with reduced circulating angiotensin-(1-7) levels in females (P<.001). Univariate linear regression analysis revealed that circulating ACE2 levels were positively associated with systolic blood pressure (P=.02), mean arterial pressure (P=.02) and serum creatinine (P<.001) in females whereas circulating ACE2 levels were positively associated with age (P<.001) and serum creatinine (P<.001) in males.. ACE2 SNPs and haplotypes are associated with circulating angiotensin-(1-7) levels. ACE2 genetic variants may be the determinants of circulating angiotensin-(1-7) levels in hypertensive females.

Topics: Aged; Alleles; Angiotensin I; Angiotensin-Converting Enzyme 2; Blood Pressure; Essential Hypertension; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Peptide Fragments; Peptidyl-Dipeptidase A; Polymorphism, Single Nucleotide

Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD.. In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney.. We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls.. Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

Topics: Adult; Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Case-Control Studies; Enzyme Inhibitors; Essential Hypertension; Female; Fibromuscular Dysplasia; Glomerular Filtration Rate; Humans; Hypertension; Hypertension, Renovascular; Male; Microvessels; Middle Aged; Nitric Oxide Synthase; Peptide Fragments; Renal Artery; Renal Circulation; Renin; Renin-Angiotensin System; Sex Factors

Angiotensin-(1-7) modulates renal blood flow in humans with essential hypertension by inducing vasodilation and counterbalancing angiotensin II-induced vasoconstriction. Little is, however, known about the effects of angiotensin-(1-7) in kidneys with atherosclerotic renal artery stenosis. We previously demonstrated that the effect of angiotensin-(1-7) is reduced in patients with increased activity of the renin-angiotensin system. As the renin-angiotensin system is also activated in kidneys with renal artery stenosis, we hypothesized that the vasodilatory effect of angiotensin-(1-7) is also reduced in such kidneys.. Therefore, we selectively measured mean renal blood flow (¹³³Xenon washout method) before and during local infusion of angiotensin-(1-7) (0.27, 0.9, and 2.7 ng/kg per min) in hypertensive patients who were angiographically evaluated for the presence of renovascular abnormalities. Data were analyzed in three groups: stenotic kidneys, nonstenotic kidneys with renal artery stenosis of the contralateral kidney (contralateral stenotic kidneys), or essentially hypertensive controls without renovascular abnormalities (matched for urinary sodium excretion).. Angiotensin-(1-7) infusion resulted in an increase in renal blood flow in matched controls. In stenotic kidneys however, the effect of angiotensin-(1-7) was significantly reduced as compared to controls. The angiotensin-(1-7) effect in contralateral stenotic kidneys was comparable to controls.. Angiotensin-(1-7)-induced vasodilation is reduced in stenotic kidneys, but not in contralateral stenotic kidneys. This suggests that the altered blood flow regulation in kidneys with atherosclerotic renal artery stenosis is a local phenomenon and not related to generalized atherosclerotic burden. Probably, the renin-angiotensin system activation, bioavailability of nitric oxide, and structural changes in the stenotic kidney play a role in this phenomenon.

Topics: Angiotensin I; Case-Control Studies; Essential Hypertension; Female; Humans; Hypertension; Kidney; Male; Middle Aged; Peptide Fragments; Renal Artery; Renal Artery Obstruction; Renal Circulation; Renin-Angiotensin System; Vasodilation