J. Levenson

Renal and systemic hemodynamics in sustained essential hypertension.

Cardiac output (CO), renal blood flow (RBF), calf blood flow (CBF), and hepatic blood flow (HBF), glomerular filtration rate (GFR), and dopamine beta hydroxylase (D beta H) activity were studied in 198 men (67 normotensive controls and 131 hypertensive patients) of the same age with sustained uncomplicated essential hypertension. In the hypertensive men, the RBF and the RBF/CO ratio were significantly decreased (p less than 0.001). The RBF and RBF/CO ratio were negatively correlated with age (p less than 0.01), blood pressure (p less than 0.01), and D beta H activity (p less than 0.01). None of these relationships were observed with CBF and HBF. The observed decreases in RBF and the RBF/CO ratio in hypertensive men were reversed after administration of clonidine and alpha-methyldopa (p less than 0.01), but not after administration of propranolol. The study provides evidence that the reduction of renal perfusion in essential hypertension is partly reversible and related to an abnormality in the adrenergic system control.

Captopril-induced changes in large arteries in essential hypertension

The effect on large arteries of the converting enzyme inhibitor captopril was studied in men with sustained essential hypertension with two different hemodynamic parameters: (1) systemic arterial compliance and (2) brachial artery diameter. After captopril administration, a 20 percent increase in arterial compliance was observed. The same increase was obtained with a 5 percent (acute experiment) and a 15 percent (short-term experiment) decrease in blood pressure, indicating that the decrease in pressure could not explain exclusively the increase in compliance. This assumption was studied with determinations of brachial artery diameter using original pulsed Doppler systems. After captopril administration, brachial artery diameter increased markedly despite the decrease in blood pressure. In addition to its effect on small arteries, the converting enzyme inhibitor captopril also has a special effect on the large arteries of patients with essential hypertension.

Blood viscosity as a chronic contributing factor of vasodilatation in humans

Since resistance to flow is theoretically determined by arteriolar geometry and blood viscosity, we studied these two factors in 44 normal and 106 hypertensive subjects. Brachial bed vascular resistance was calculated as the ratio between mean pressure and brachial artery flow. Systemic blood viscosity in vitro was determined at 96 per s, while microvessel blood viscosity in vivo was estimated from the haematocrit-viscosity relationship at 240 per s. A resistive radius index was calculated which was only related to the microvessel viscosity: resistance ratio. Compared to normal subjects, hypertensive subjects had higher systemic in vitro blood viscosity (4.75 +/- 0.47 versus 4.50 +/- 0.43 mPa.s; P less than 0.005) and microvessel blood viscosity (2.60 +/- 0.21 versus 2.43 +/- 0.16 mPa.s; P less than 0.001). Hypertensive subjects also had a higher brachial vascular resistance (161 +/- 89 versus 124 +/- 58 mmHg/ml per s; P less than 0.01), but showed a similar resistive radius index (2.47 +/- 0.36 versus 2.57 +/- 0.35) compared to normal subjects. There was a positive correlation between systemic viscosity and brachial artery diameter and a negative correlation between microvessel viscosity and vascular resistance in the normotensive (P less than 0.05 and P less than 0.001, respectively) and hypertensive groups (P less than 0.001 and P less than 0.005, respectively). The resistive radius index was positively related to viscosity in normal and in hypertensive groups (P less than 0.001) but these relationships were significantly different (P less than 0.001), showing that, at the highest viscosities, arterial radius increased less in hypertensive than in normal subjects. Thus, the level of blood viscosity might influence arterial diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracellular Fluid Volume and Renal Indices in Essential Hypertension

Extracellular fluid volume (EFV), total blood volume (TBV), and renal indices were determined in 53 permanent essential hypertensive patients with normal renal function and balanced sodium intake and urinary output. In comparison with normal subjects, hypertensives had normal EFV values while TBV and the TBV/EFV ratio were significantly reduced (p less than 0.001). In hypertensives, a significant negative relationship (r = -0.40; p less than 0.005) was observed between the TBV/EFV ratio and diastolic arterial pressure. No correlation existed between TBV and diastolic pressure, whereas EFV (and also interstitial fluid volume) was positively related to diastolic arterial pressure (r = +0.41; p less than 0.005). Extracellular fluid volume and interstitial fluid volume were both directly correlated to the renal filtration fraction (r = +0.45; p less than 0.005). The study suggests that, in the disturbed partition of the extracellular fluid of hypertensives, changes in the interstitial space are involved and are related to variations in the renal indices.

Plasma cGMP and Large Artery Remodeling in Asymptomatic Men

cGMP regulates vascular smooth muscle tone and arterial wall response to proliferative signals. We determined plasma cGMP and carotid artery intima-media thickness (IMT) and diameter in 84 asymptomatic men submitted to investigation of their cardiovascular risk profiles. Plasma cGMP was positively associated with IMT (P<0.01) and diameter (P<0.05), independently of coexisting risk factors. These associations were reinforced in the subgroup of subjects with high-sensitivity C-reactive protein level or multiple atherosclerotic plaques. A positive relationship existed between diameter and IMT (P<0.01) and disappeared after cGMP adjustment. This suggests a link between cGMP pathway and arterial wall geometry that is revealed by vascular injury conditions and may participate in early large artery remodeling.

Effect of cadralazine on brachial artery hemodynamics and forearm venous tone in essential hypertension

Forearm venous tone and brachial artery hemodynamics, including determinations of the arterial diameter and compliance by the use of pulsed Doppler systems, were measured in 16 patients with sustained essential hypertension before and after acute oral cadralazine dosing. Systolic and diastolic blood pressures significantly decreased, whereas heart rate increased. Brachial artery diameter and vascular resistance decreased, respectively, from 0.501 ± 0.015 to 0.485 ± 0.015 cm (P < 0.001) and from 124.8 ± 13.8 to 99.3 ± 11.9 mm Hg/ml · sec (P < 0.01). Blood flow velocity increased (P < 0.05) but volumic flow, pulse wave velocity, and brachial artery compliance did not change. Forearm venous tone increased but the increase was inversely related to the degree of arteriolar vasodilatation. Our results indicate that, with cadralazine, (1) forearm vascular resistance decreased while forearm blood flow was unchanged, (2) the dilatation of small arteries contrasted with a significant reduction in the diameter of the large brachial artery, and (3) the decrease in blood pressure was associated with a lack of increase in arterial compliance and changes in venous tone. This suggests an overriding influence of the activation of the autonomic nervous system on the action of cadralazine on large arteries and veins.

Effects of Beta-Adrenergic Blockade on the Arterial Vasculature in Essential Hypertension

The effect of beta-blockade was studied in 3 different kinds of human hypertension: borderline, sustained and isolated systolic hypertension. Young patients with borderline hypertension had a similar decrease in cardiac output with both nonselective and selective beta-blockade. Only nonselective beta-blockade decreased brachial artery blood flow and increased forearm vascular resistance. In patients with sustained essential hypertension, chronic administration of 2 nonselective beta-blockers, propranolol and pindolol, caused a similar significant decrease in blood pressure with different effects on forearm circulation. Pindolol produced a significant vasodilation of both large and small arteries of the forearm while propranolol did not. In patients with isolated systolic hypertension, short-term beta-adrenergic blockade with propranolol had different effects according to age. In younger patients, propranolol significantly decreased systolic pressure with a concomitant increase in rapid ventricular ejection. In older patients, a lack of systolic pressure reduction was observed with an increase in total peripheral resistance and a decrease in systemic arterial compliance. The results suggested that beta-adrenergic blockade in hypertension may affect blood vessels with different effects, according to age, to the characteristics of hypertension and to the specific properties of the beta-blocking agent. The vascular effects involve not only resistive vessels but also large arteries.

Influence of hypercholesterolemia and endothelin-3 pre-treatment on the effects of shear forces on platelet aggregation and cyclic GMP content

Shear forces induce platelet aggregation and stimulate the endothelial production of anti-aggregatory factors. Among them, endothelin-3 (ET-3) has been reported to reduce aggregation and to increase platelet cyclic GMP (cGMP) content. Since hypercholesterolemia modifies both platelet aggregability and endothelial function, we compared in 14 hypercholesterolemic and 15 normocholesterolemic subjects the influences of shear forces (240 and 650 s(-1)) on platelet aggregation and cGMP content, and their modulation by ET-3. Spontaneous maximal aggregation occurred earlier and at a greater extent in hypercholesterolemic than in normocholesterolemic subjects (63+/-2 vs 46+/-6% P < 0.01). Pre-treatment with ET-3 abolished the shear-induced facilitation of maximal aggregation in platelets of normocholesterolemic (from 70+/-2 to 52+2% at 240 s(-1) and from 73+/-1 to 59+/-2S at 650s(-1); P < 0.05) and hypercholesterolemic (from 78+/-3 to 64+/-2 at 240 s(-1) and from 78+/-2 to 66+/-3 at 650 s(-1); P < 0.05) subjects. cGMP content did not significantly differ between normocholesterolemic and hypercholesterolemic subjects (6.1+/-0.5 vs 6.9+/-0.7 pmol/10(9) platelets). It was reduced in platelets submitted to shear forces (P < 0.05). This shear-dependent reduction was suppressed by ET-3 pre-treatment. These results demonstrate that shear forces enhance platelet aggregation and diminish their cGMP content. ET-3 reduces the pro-aggregating effects of shear, suggesting a rise in cGMP content as a dynamic associated mechanism.