Gene-Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the Antihypertensive Effects of Enalapril.

Protein kinase C (PKC) signalling is critically involved in the control of blood pressure. Angiotensin-converting enzyme inhibitors (ACEi) affect PKC expression and activity, which are partially associated with the responses to ACEi. We examined whether PRKCA (protein kinase C, alpha) polymorphisms (rs887797 C>T, rs1010544 T>C and rs16960228 G>A), or haplotypes, and gene-gene interactions within the ACEi pathway affect the antihypertensive responses in 104 hypertensive patients treated with enalapril as monotherapy.

Endothelial nitric oxide synthase tagSNPs influence the effects of enalapril in essential hypertension.

The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are associated with up-regulation of endothelial nitric oxide synthase (NOS3) activity. This mechanism may explain how polymorphisms in NOS3 gene affect the antihypertensive responses to ACEi. While clinically relevant NOS3 polymorphisms were previously shown to affect the antihypertensive responses to enalapril, no study has tested the hypothesis that NOS3 tagSNPs influence the antihypertensive effects of this drug.

Association of Mineralocorticoid Receptor Polymorphism I180V With Left Ventricular Hypertrophy in Resistant Hypertension.

Objectives: Genetic polymorphisms on mineralocorticoid receptor gene (NC3C2) are associated with variability of mineralocorticoid receptor (MR) function and cardiovascular implications. We sought to investigate whether I180V (rs5522) and MRc.-2G_C (rs2070951) polymorphisms in NR3C2 gene are associated with resistance to antihypertensive treatment and target-organ damage in resistant hypertensive (RHTN) patients.

Effects of angiotensin-converting enzyme inhibition on leptin and adiponectin levels in essential hypertension.

Activation of the renin-angiotensin-aldosterone system (RAAS) and abnormal adipokine levels are biological alterations that affect blood pressure regulation and interact to link hypertension, obesity and metabolic diseases. While imbalanced levels of hormones produced by adipocytes including hypo-adiponectinaemia and hyperleptinaemia were reported in hypertension, little is known about how antihypertensive therapy affects these alterations. This study aimed to evaluate the effects of enalapril on plasma adiponectin and leptin levels in hypertensive individuals.

Comprehensive evaluation of the effects of enalapril on matrix metalloproteinases levels in hypertension.

Purpose: Angiotensin-converting enzyme inhibitors (ACEi) may downregulate matrix metalloproteinases (MMPs). We examined whether enalapril affects MMP-2, MMP-8, and MMP-9 levels and activity, and their endogenous inhibitors (tissue inhibitors of MMPs, TIMP-1 and TIMP-2) levels in hypertensive patients. Moreover, we assessed the effects of enalaprilat on MMP-9 and TIMP-1 secretion by human endothelial cells (HUVECs).

Consistent alterations of circulating matrix metalloproteinases levels in untreated hypertensives and in spontaneously hypertensive rats: a relevant pharmacological target.

Inconsistent matrix metalloproteinases (MMPs) levels have been reported in hypertension, with higher, similar and lower MMPs levels reported in hypertensives compared with normotensives. Differences between studies may reflect lack of control of drug effects, accompanying diseases and pre-analytical issues. We compared MMP-2, MMP-8 and MMP-9 levels in 38 untreated hypertensive patients (with no other diseases) with those found in 33 normotensive controls.

Antihypertensive effects exerted by enalapril in mild to moderate hypertension are not associated with changes in the circulating levels of nitric oxide-related markers.

Purpose: The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are explained, at least in part, by enhanced bradykinin-dependent nitric oxide (NO) formation and decreased angiotensin II-induced oxidative stress and vasoconstriction. We examined for the first time whether treatment with enalapril increases the plasma levels of markers of NO formation and decreases oxidative stress in mild to moderate hypertensive patients.

Methods: Eighteen untreated hypertensive patients were treated with enalapril 10 mg/day (n=10) or 20 mg/day (n=8) for 60 days.