Correlation of pulse wave velocity with left ventricular mass in patients with hypertension once blood pressure has been normalized

Vascular stiffness has been proposed as a simple method to assess arterial loading conditions of the heart which induce left ventricular hypertrophy (LVH). There is some controversy as to whether the relationship of vascular stiffness to LVH is independent of blood pressure, and which measurement of arterial stiffness, augmentation index (AI) or pulse wave velocity (PWV) is best. Carotid pulse wave contor and pulse wave velocity of patients (n=20) with hypertension whose blood pressure (BP) was under control (<140/90 mmHg) with antihypertensive drug treatment medications, and without valvular heart disease, were measured. Left ventricular mass, calculated from 2D echocardiogram, was adjusted for body size using two different methods: body surface area and height. There was a significant (P<0.05) linear correlation between LV mass index and pulse wave velocity. This was not explained by BP level or lower LV mass in women, as there was no significant difference in PWV according to gender (1140.1+67.8 vs 1110.6+57.7 cm/s). In contrast to PWV, there was no significant correlation between LV mass and AI. In summary, these data suggest that aortic vascular stiffness is an indicator of LV mass even when blood pressure is controlled to less than 140/90 mmHg in hypertensive patients. The data further suggest that PWV is a better proxy or surrogate marker for LV mass than AI and the measurement of PWV may be useful as a rapid and less expensive assessment of the presence of LVH in this patient population

Impaired sodium excretion during mental stress in mild essential hypertension

In hypertensive rats, environmental stress causes sodium retention by an exaggerated increase in renal sympathetic nerve activity, which is modulated by angiotensin II. We tested whether similar effects can be observed in humans. In 66 normotensive subjects (half of them with a family history of hypertension) and 36 subjects with mild essential hypertension, urinary sodium excretion and renal hemodynamics were examined at rest and during mental stress treated either with placebo or ACE inhibition in a double-blind, randomized, cross-over design. Despite a marked increase in glomerular filtration rate in response to mental stress (Deltaglomerular filtration rate, 4.3+/-7.7 mL/min in normotensives without versus 5.6+/-8.4 mL/min in normotensives with a family history versus 10.1+/-5.7 mL/min in patients with mild essential hypertension; P:&#60;0.002), the increase in urinary sodium excretion was blunted in patients with mild essential hypertension (Deltaurinary sodium excretion, 0.12+/-0.17 mmol/min versus 0.10+/-0.14 mmol/min versus 0.05+/-0.14 mmol/min; P:&#60;0.05). ACE inhibition corrected the natriuretic response to mental stress in subjects with mild essential hypertension (Deltaurinary sodium excretion, 0.05+/-0.14 mmol/min with placebo versus 0.13+/-0.19 mmol/min with ACE inhibition; P:&#60;0.01); thus, after ACE inhibition, urinary sodium excretion increased similarly in all 3 groups. In conclusion, impaired sodium excretion occurs during mental stress in human essential hypertension but not in subjects with positive family history of hypertension. This abnormality in sodium handling during activation of the sympathetic nervous system appears to be mediated by angiotensin II

Effect of AT1 receptor blockade on endothelial function in essential hypertension

Background: Angiotensin II adversely affects endothelial function and NO availability. We analyzed the effect of AT1 receptor blockade on endothelium-dependent vasodilation and basal nitric oxide (NO) production and release in hypertensive patients. &lt;p&gt;&lt;/p&gt; Methods and results: Sixty patients (53 ± 10 years) with essential hypertension were randomized to 6 weeks of double-blind therapy with either valsartan (80 mg), hydrochlorothiazide (HCTZ) (25 mg), or placebo once daily. Basal NO production and release was assessed by measuring forearm blood flow (FBF) in response to intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA), and endothelium-dependent vasodilation by measuring FBF in response to intra-arterial administration of acetylcholine, respectively. Intra-arterial infusion of noradrenaline and sodium nitroprusside was used to assess endothelium-independent changes in FBF. Blood pressure (BP) similarly decreased with active treatments (P &#60; .001). After valsartan treatment, the decrease of FBF in response to L-NMMA was augmented (4 μmol/min L-NMMA, −1.3 ± 1.2 after v −0.5 ± 1.1 mL/min/100 mL before therapy, P &#60; .02; 8 μmol/min L-NMMA: −1.7 ± 1.3 after v −1.1 ± 1.2 mL/min 100 mL before therapy, P &#60; .05). No improvement was found after placebo or HCTZ treatment. Changes in L-NMMA-induced decrease of FBF with valsartan treatment were not related to BP changes. Neither drug substantially modified the response of FBF induced by intra-arterial infusion of acetylcholine, noradrenaline, and sodium nitroprusside. &lt;p&gt;&lt;/p&gt; Conclusions: The AT1 receptor blockade with valsartan improved basal NO production and release. The effect seems to be BP independent, as BP reduction with HCTZ failed to increase NO availability

Vitamin C augments the renal response to L-arginine in smokers

&lt;p&gt;Background: In the coronary and the forearm circulations, endothelium-dependent vasomotion is impaired in smokers, but can be augmented by l-arginine or vitamin C. We examined whether smoking similarly affects the renal circulation.&lt;/p&gt; &lt;p&gt;Methods: In 20 smokers (age 26 ± 4 years) and in 20 non-smokers (age 28 ± 3 years) changes of renal plasma flow (RPF), glomerular filtration rate (GFR), blood pressure and heart rate in response to the subsequent intravenous infusions of NG-monomethyl-l-arginine (L-NMMA), l-arginine and l-arginine plus vitamin C were studied by use of a constant infusion input clearance technique.&lt;/p&gt; &lt;p&gt;Results: Systemic haemodynamic parameters did not differ between smokers and non-smokers during each experimental phase. At baseline, RPF and GFR were similar between the groups. The infusion of L-NMMA led to a similar decrease of RPF, while GFR did not change in either group. During the infusion of l-arginine RPF increased similarly. Finally, the co-infusion of l-arginine plus vitamin C led to a significantly greater increase of RPF (+277 ± 395 vs +79 ± 76 ml/min, P = 0.03) and GFR (+12.1 ± 10.6 vs +3.4 ± 11.2 ml/min, P = 0.02) in smokers as compared to non-smokers.&lt;/p&gt; &lt;p&gt;Conclusions: L-NMMA-induced vasoconstriction of the renal vasculature was similar in smokers compared to non-smokers. l-arginine alone induced a similar increase of RPF. The co-infusion of vitamin C and l-arginine led to a greater increase of RPF and GFR in smokers. This might suggest that oxidative stress is increased in the renal vasculature of smokers.&lt;/p&gt

Direct comparison of the effects of valsartan and amlodipine on renal hemodynamics in human essential hypertension

&lt;p&gt;Background: To elucidate the renoprotective mechanism of AT1-receptor blockers, we compared the effects of the AT1-receptor blocker valsartan with those of the calcium channel blocker amlodipine on renal hemodynamics and microcirculation.&lt;/p&gt; &lt;p&gt;Methods: A total of 58 patients (50.2 ± 9.0 years) with mild to moderate essential hypertension were included in a randomized, double-blind study to receive either valsartan (80 to 160 mg) or amlodipine (5 to 10 mg). Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured before and after 8 weeks of treatment. Glomerular hydrostatic pressure (PGlo) and resistances of the afferent (RA) and efferent (RE) arterioles were calculated according to the Gomez formulas.&lt;/p&gt; &lt;p&gt;Results: Blood pressure control was similar in both groups. RPF did not change with either treatment. In contrast, GFR increased with amlodipine (+8 ± 14 mL/min; P &#60; .01) but was preserved with valsartan. Amlodipine caused a more marked increase in the RE/RA ratio than valsartan (+0.26 ± 0.26 v +0.13 ± 0.24, P &#60; .05), which was paralleled by an increase in PGlo in patients treated with amlodipine (+1.9 ± 4.3 mm Hg; P &#60; .05) but not in those treated with valsartan.&lt;/p&gt; &lt;p&gt;Conclusions: At similar blood pressure control, valsartan maintained GFR and PGlo, whereas amlodipine led to glomerular hyperfiltration and an increase in PGlo. The results might explain the favorable renal outcome with AT1-receptor blocker therapy.&lt;/p&gt

AT1-receptor blockade improves augmentation index: a double-blind, randomized, controlled study

Objective : Arterial hypertension leads to vascular structural and functional adaptive processes that are influenced by angiotensin II. To analyze the effects of AT1 receptor blockade on vascular function we determined augmentation index. &lt;p&gt;&lt;/p&gt; Methods and design : A total of 60 patients (53 ± 10 years) with essential hypertension mean [blood pressure (BP) 173 ± 9/102 ± 3 mmHg] were randomized to 6 weeks double-blind therapy with either valsartan 80 mg, hydrochlorothiazide (HCTZ) 25 mg or placebo once daily. Radial artery pressure wave was determined by applanation tonometry before and after therapy. The central aortic pressure wave and augmentation index were derived by a generalized transfer function. &lt;p&gt;&lt;/p&gt; Results : Active therapy similarly reduced systolic and diastolic blood pressure (SBP, DBP) (valsartan: -22 ± 18/-11 ± 11 mmHg, HCTZ: -22 ± 23/-14 ± 14 mmHg, all P &#60; 0.001). However, only valsartan, but no HCTZ reduced the augmentation index (valsartan: from 148 ± 18 to 126 ± 24, P &#60; 0.001; HCTZ: from 145 ± 19 to 142 ± 18, NS). Augmentation index reduction was greater with valsartan (-22 ± 11) than with HCTZ (-3 ± 11) and placebo (0 ± 13) (P &#60; 0.01 for pairwise comparison of valsartan versus HCTZ and placebo after Bonferroni correction). Differences remained significant after taking changes in supine BP into account (covariance, P &#60; 0.01). &lt;p&gt;&lt;/p&gt; Conclusions : Blood pressure reduction with the AT1 receptor antagonist valsartan but not with hydrochlorothiazide reduced the augmentation index in essential hypertension

Plasma endothelin is increased in early essential hypertension

Local vascular generation of endothelin-1 (ET-1) may contribute to elevated peripheral resistance in hypertension. We tested the hypothesis that immunoreactive ET production in the forearm circulation is increased in early essential hypertensive subjects. Ten young, previously untreated male patients with mild essential hypertension and no signs of target organ damage were compared with matched normotensive subjects in an outpatient setting. Arterial and venous samples were obtained from indwelling catheters in the brachial artery and the medial cubital vein, respectively. Samples were collected at baseline and after induction of endothelium-dependent (acetylcholine) vasodilation. Immunoreactive ET (ET) was measured after column extraction by a sensitive radioimmunoassay employing a C-terminal ET-1 antibody with negligible cross-reaction to big-ET. Individual recovery rates were determined for each sample. Basal ET was significantly higher in hypertensive than in normotensive subjects, both in venous and arterial samples (P &lt; .01). This difference was also present after correction for recovery (P &lt; .01). There was no significant difference between venous and arterial ET concentrations. Local vasodilation did not change arterial or venous ET levels. In conclusion, plasma ET is increased in young, untreated, essential hypertensive subjects with no signs of target organ damage. The increased circulating immunoreactive ET may point to a role for the peptide early in the development of high blood pressure

Altered aldosterone response to salt intake and angiotensin II infusion in young normotensive men with parental history of arterial hypertension

Our findings suggest that young normotensive subjects with parental history of arterial hypertension are characterized by an inadequate suppression of aldosterone production in response to salt loading and an exaggerated and prolonged hyper-responsiveness of aldosterone secretion in response to Ang II. This might contribute to the increased risk for the development of essential hypertension in subjects with positive family history of arterial hypertension

Effect of irbesartan versus atenolol on left ventricular mass and voltage: results of the Cardio Vascular Irbesartan Project

Regression of hypertensive left ventricular hypertrophy (LVH) is associated with improved prognosis. The aim of this trial was to compare the effects of irbesartan versus atenolol on LVH in subjects with essential hypertension. Because electrocardiographic and echocardiographic parameters of LVH carry disparate prognostic information, both methods were applied in this trial. In the randomized, double-blind, multicenter trial CardioVascular Irbesartan Project, 240 patients with essential hypertension were treated with irbesartan or atenolol for 18 months. Voltage criteria used for LVH were Sokolow index, Cornell index, Cornell voltage x QRS duration product and Lewis index. In parallel, left ventricular mass (LVM) was determined by 2-dimensional guided M-mode echocardiography. After 6 and 18 months, reductions of LVM and voltage criteria for LVH were only found in subjects treated with irbesartan. However, a reduction of LVM was only detectable in subjects within the highest quartile of baseline LVM but not overall. In contrast, reductions of voltage criteria for LVH were detectable after 6 and 18 months even within commonly used normal limits. In conclusion, treatment of hypertension with irbesartan resulted in a significant reduction in the voltage criteria for LVH, although an effect on LVM was only seen in subjects with high baseline LVM. In contrast, atenolol did not lead to reductions in electrocardiographic or echocardiographic parameters of LVH. Because voltage criteria for LVH have been shown to predict cardiovascular outcome independently from LVM, we suggest that both methods should be used to accurately assess the benefits of antihypertensive treatment