Angiotensin-Converting Enzyme Gene Polymorphism Is Associated With Endothelium-Dependent Vasodilation in Never Treated Hypertensive Patients

Abstract

Abstract-The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 g/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 g/min, each for 5 minutes) was evaluated in 32 never-treated hypertensive outpatients (17 men and 15 women, aged 43Ϯ7 years) and in 24 normotensive control subjects (14 men and 10 women, aged 42Ϯ6 years). Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. In both hypertensive and normotensive groups, a deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene was determined by polymerase chain reaction. The response to acetylcholine was significantly reduced in hypertensive patients versus control subjects: at the highest dose (30 g/min), forearm blood flow was 13.9Ϯ6.3 mL ⅐ 100 mL tissue Ϫ1 ⅐ min Ϫ1 in hypertensives versus 27.1Ϯ9.7 mL ⅐ 100 mL tissue Ϫ1 ⅐ min Ϫ1 in the controls (PϽ.001); similarly, vascular resistance was 10.6Ϯ5.6 U in hypertensive patients and 4.9Ϯ1.9 U in normotensive subjects. In the hypertensive group, the patients with DD genotype showed significantly less endothelium-dependent vasodilation compared with IDϩII genotypes (at the highest dose of acetylcholine, forearm blood flow was 12.1Ϯ4.2 versus 17.0Ϯ4.1 mL ⅐ 100 mL tissue Ϫ1 ⅐ min Ϫ1 ) (PϽ.005). The vasodilator effect of sodium nitroprusside infusions was not statistically different in DD and IDϩII hypertensive patients. In conclusion, our data suggest that ACE polymorphism affects endothelium-dependent vasodilation in hypertensive patients and confirm that hypertensive patients had a blunted response to the endothelium-dependent agent acetylcholine. (Hypertension. 1998;31:900-905.) Key Words: angiotensin-converting enzyme Ⅲ polymorphism Ⅲ endothelium Ⅲ hypertension, essential T he normal endothelium plays a key role in modulating vascular tone, preventing thrombosis, and influencing smooth muscle growth.1 The EDRF identified as nitric oxide [2][3][4][5] induces vasodilation by stimulating the activity of soluble guanylate cyclase within the vascular smooth muscle, thereby elevating tissue levels of cyclic GMP. 4 On the other hand, SNP induces endothelium-independent vasodilation through the same effector pathway by providing an inorganic source of nitric oxide. 6 Recent studies in humans have confirmed these experimental findings and have demonstrated that this regulatory action of the endothelium is exerted on resistance vessels also. However, this endothelial function is impaired in different cardiovascular diseases 8 -17 ; in particular, ACh vasodilation is reduced in hypertensive patients compared with normotensive control subjects.In addition, the RAS seems to be involved in the pathophysiology of hypertension by regulating BP, as well as fluid and electrolyte balance. For these reasons, genes coding for components of this system are attractive candidates for the investigation of the genetic basis of essential hypertension. The cloning of the ACE gene has made it possible t...

Genetic polymorphisms influence runners’ responses to the dietary ingestion of antioxidant supplementation based on pequi oil (Caryocar brasiliense Camb.): a before-after study

“…The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure (BP), fluid and electrolyte homeostasis, and cardiovascular and renal pathophysiologic processes [24,106]. For these reasons, genes coding for components of this system are attractive candidates for the investigation of the genetic basis of essential hypertension [106] and for the elucidation of the pathogenesis of CVD [25].…”

Exclusion of the ACE D/I Gene Polymorphism as a Determinant of Endothelial Dysfunction

“…30,48 Recent data have, however, been published that suggest the D allele could be a cause or a marker of impaired endothelium-dependent vasodilatation, thereby providing a clue to the potential mechanisms accounting for the increased risk of CVD. 37,38 To further address this possibility, we used venous occlusion plethysmography in a relatively large population of mild-to-moderate primary hypertensive patients, most of whom had never been previously treated, and in a group of healthy normotensive subjects. All underwent careful genotyping for the ACE D/I polymorphism and determination of the FBF response to the local administration of the endothelium-dependent vasodilator ACh and of the endothelium-independent vasodilator SNP.…”

“…33,34 According to Perticone et al, 37 who studied a smaller population of nevertreated primary hypertensive patients (nϭ32) and normotensive control subjects (nϭ24), the DD genotype would be associated with significant blunting of endotheliumdependent vasodilatation but not of endothelium-independent vasodilatation. More recently, a blunted endotheliumdependent vasodilatation was reported in healthy young normotensive university students (nϭ68) carrying the D allele compared with II homozygous subjects.…”

Working under pressure: the vascular endothelium in arterial hypertension

“…45,47,49,[211][212][213][214][215][216][217][218][219][220][221] The multifactorial aetiology of essential hypertension as well as the duration of blood pressure elevation may explain certain inconsistent results of different investigators. 222,223 Besides certain ACE-inhibitors, several calcium channel blocking agents were successful in improving endothelial function in human hypertension (Table 1). Antioxidative properties of an antihypertensive drug are important, since oxidative stress plays a central role in the pathophysiology of human hypertension.…”