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Hemodynamic parameters were studied before and after rapid dextran infusion in 34 men including 17 patients with sustained essential hypertension and 17 normotensive controls. In both groups of patients, dextran infusion induced a significant increase (p less than 0.001) in central venous pressure (CVP), cardiac output (CO), and stroke volume. The percent change in stroke volume was significantly higher in hypertensives (p less than 0.001) than in controls. Three indices of volume expansion were calculated: 1) the ratio between the change in CO and the change in volume, which was significantly higher in hypertensives (p less than 0.025), 2) the ratio between the change in CO and the change in CVP, which was similar in both groups, and 3) the ratio between the change in volume and the change in CVP, which was significantly reduced in hypertensives (p less than 0.001). In the overall population, the latter ratio was negatively correlated with the change in CO (or in stroke volume) induced by expansion ( r = -0.75). The results provided evidence that: 1) the slope of the relationship between CO and blood volume was steeper in hypertensives than in normotensives, and 2) the steeper slope was due to a reduction in the effective compliance of the vascular bed, causing a greater elevation in CO per unit rise in volume.

The effects of a single oral dose of 20 mg of nicorandil were evaluated in 12 untreated patients with mild to moderate essential hypertension. Serial measurements of arterial pressures were obtained by means of an automatic device (Dynamap) up to 120 minutes after drug administration. Forearm hemodynamics were determined with a pulsed Doppler velocimeter, or strain gauge mecanography and plethysmography enabling measurement of the diameter, velocity and flow of the brachial artery as well as the arterial pulse wave velocity and forearm venous tone. In addition, local vascular resistance, compliance and impedance were deduced. Nicorandil administration produced a significant decrease in systolic and diastolic blood pressure, from 18 minutes after dosing which lasted up to the end of the study (i.e., 120 minutes after drug administration) (p less than 0.01). This decrease in blood pressure was not associated with reflex tachycardia. The brachial artery diameter increased significantly (p less than 0.01) with no change in brachial artery blood flow. A decrease in brachial-radial pulse wave velocity and arterial impedance (p less than 0.01) and an increase in arterial compliance were observed. Thus, this study demonstrated an antihypertensive activity of a single oral administration of nicorandil without baroreflex activation. This decrease in blood pressure was associated with a dilation of peripheral large arteries leading to an increase in arterial compliance. Thus, clinical testing to evaluate the antianginal activity of nicorandil, especially in hypertensive patients with coronary heart disease, should be encouraged.

Pharmacokinetics of isosorbide dinitrate (ISDN) and brachial arterial hemodynamics have been studied in 15 patients with sustained essential hypertension. The hemodynamic study was performed by using a pulsed Doppler device enabling evaluation of the diameter of the brachial artery with an error of less than 10%. After intravenous administration until plateau concentrations were reached, the ISDN infusion was stopped in order to study the disappearance curve of the drug and the pharmacokinetic parameters. ISDN caused a significant decrease in systolic pressure, a significant increase in arterial diameter, and no change in heart rate. Brachial hemodynamics were not correlated with the plasma concentration in the steady state or the area under the disappearance curve. In contrast, the changes in arterial diameter during perfusion were significantly correlated with the apparent distribution volume, a finding that might indirectly reflect the affinity of ISDN for vascular tissues.

Arterial compliance was determined in eight normal subjects and 23 patients with hypertension and vascular disease by two independent techniques: (a) with a plethysmographic strain gauge (to measure pulsatile forearm volume changes as representing intra-arterial volume changes) and an automated sphygmomanometric system (to measure pulse pressure) and (b) calculation from the local pulse wave velocity and dimension of the brachial artery measured by pulsed wave Doppler ultrasound. Arterial compliance measured both by the plethysmographic technique and calculated from the pulse wave velocity was reduced in subjects with hypertension and vascular disease as compared with normal subjects. The regression equation between the compliance determined by the plethysmographic technique (x) and that calculated (y) from the pulse wave velocity and brachial arterial diameter was y = 3. 35x + 1.53, r = 0.77, P less than 0.001. The good correlation appears to validate the plethysmographic technique as a method of determining arterial compliance.

Acute effects of a new calcium entry blocker, nitrendipine, on large arteries of the forearm were studied by using arterial pulse strain gauge mecanography and pulsed Doppler velocimetry of the brachial artery in 13 mild to moderate essential hypertensive patients. Ninety minutes after nitrendipine ingestion, patients exhibited significant decreases in blood pressure without changes in heart rate; increases in brachial artery diameter and decreases in brachial to radial pulse wave velocity; increases in arterial compliance and decreases in characteristic impedance; and increases in brachial artery blood velocity and flow and decreases in forearm vascular resistance. Lastly, amplitude of pulse pressure was decreased by nitrendipine and negatively correlated to the level of arterial compliance. These results suggest that nitrendipine exerts a direct benefit effect on the hypertensive large arteries whose two main consequences are a decrease in pulsatility of arterial pressure and an increase in arterial flow.

Echocardiographic dimensions and hemodynamic indexes were determined in 42 patients with borderline hypertension and in 22 with sustained hypertension and the results were compared with findings in 33 normal subjects. In patients with borderline hypertension the thickness of the interventricular septum (IVS) was significantly increased (P less than 0.001), whereas the posterior wall PW) thickness remained within normal range. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). In patients with sustained hypertension a symmetric cardiac hypertrophy was observed, and there was a significant positive correlation between the IVS/PW ratio and diastolic pressure (P less than 0.05). The study suggested that (1) in sustained hypertension the symmetric cardiac hypertrophy was secondary to a progressive increase in pressure load, whereas (2) in borderline hypertension the asymmetric cardiac hypertrophy could not be directly related to the level of blood pressure and was probably associated with abnormalities of the sympathetic nervous system.

The relationship between cardiac hypertrophy, ventricular function, and aortic volume distensibility was studied in men with sustained essential hypertension by echocardiography and determination of pulse-wave velocity. The more reduced the aortic distensibility, the higher was the blood pressure response to exercise and the greater were the degree of cardiac hypertrophy and the modifications in systolic time intervals. Changes in cardiac performance as determined by vasodilators equipotent in relation to blood pressure reduction were found to have markedly different effects on aortic distensibility; volume distensibility was unchanged by cadralazine but was improved by calcium entry blockers and isosorbide dinitrate. Our findings suggest that alterations in the buffering function of the large arteries, as indicated by decreased volume distensibility, participate in the increased afterload in patients with essential hypertension and thus influence the degree of cardiac hypertrophy and changes in cardiac function and selective use of antihypertensive drugs may influence cardiovascular morbidity and mortality by their differential effect on large-vessel distensibility.

Systolic time intervals, echocardiographic dimensions and hemodynamic parameters were determined in 42 borderline hypertensive patients with high cardiac output and 33 normal subjects. In borderline hypertensive patients, the preejection period was significantly reduced (P less than 0.001) and was negatively correlated to cardiac index (P less than 0.001). The interventricular septum thickness (IVS) was significantly increased (P less than 0.001) while the posterior wall thickness (PW) was within normal values. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). These findings suggest that (i) myocardial hypertrophy and increased left ventricular performance exist in borderline hypertension, (ii) myocardial contractility is reduced as myocardial hypertrophy increases.

Brachial artery diameter (pulsed Doppler method), forearm vascular resistance, and venous tone (plethysmographic method) were studied in 18 patients with sustained essential hypertension. Hemodynamic parameters were reevaluated after 3 months of treatment by propranolol (9 patients) or pindolol (9 patients). For the same decrease in pressure, propranolol decreased heart rate significantly while pindolol did not, indicating the role of intrinsic sympathomimetic activity. After pindolol, forearm vascular resistance and venous tone significantly decreased while brachial artery cross-sectional area significantly increased. After propranolol, forearm vascular resistance and brachial artery cross-sectional area did not change significantly, while forearm venous tone increased markedly. The study shows that, in the long term, pindolol dilates small and large arteries and veins of the forearm circulation whereas Propranolol apparently does not.

Repeat hemodynamic determinations were performed in 37 young men with borderline hypertension. The duration of the follow up study was 47 +/- three months. At each determination, those with borderline hypertension were compared to a group of matched normal subjects. Blood pressure increased from the first to the second determination, but the increase was significant only for systolic (P less than 0.001) and mean (P less than 0.01) arterial presssures. Cardiac index and heart rate, which were initially increased, decreased significantly (P less than 0.02; P less than 0.01, respectively) and decreased to normal values; total peripheral resistance increased (P less than 0.01); blood and plasma volumes decreased (P less than 0.01). At the first determination, the cardiac index-heart rate correlation was significant (P less than 0.01) and the cardiac index-blood volume correlation was not. At the second determination, on the contrary, the cardiac index-total blood volume correlation was significant (P less than 0.001) whereas the cardiac index-heart rate correlation was not. The study provides evidence that patients with borderline hypertension, over a short-term period, show (1) a greater increase in systolic than in diastolic pressure, (2) a return of cardiac output toward normal values through a decrease both in heart rate and blood volume, and (3) an increased importance of volume factors in the cardiac output control.

The effects of pindolol were studied on the large arteries, arterioles, and veins of the forearm in 13 patients with essential hypertension after 12 weeks of dosing. The methods used were pulsed Doppler velocimetry of the brachial artery and strain gauge mercury-in-silicone rubber plethysmography of the forearm. Compared with placebo baseline values, chronic pindolol significantly decreased systolic and diastolic blood pressure (P less than 0.001), pulse pressure (P less than 0.001), and pulse rate (P less than 0.05). A significant increase was observed in brachial artery diameter (P less than 0.01), brachial artery blood flow and velocity (P less than 0.001), and forearm arterial flow (P less than 0.001). Forearm vascular resistance and venous tone were decreased (P less than 0.001 and P less than 0.05, respectively), whereas forearm arterial compliance was increased (P less than 0.001). These results demonstrate a dilatory effect on large and small peripheral arteries and on veins of pindolol after chronic dosing, which leads to improvement in the conduction and buffering arterial function of the forearm.

1. Blood pressure, blood volume and renal blood flow were determined in 101 men; forty-three were normal subjects and fifty-eight were untreated permanent essential hypertensive patients with normal renal function and equilibrated sodium balance. 2. A significant negative pressure-volume relationship was observed overall. The relationship could be expressed as a hyperbola whose slope expressed the reduction in blood volume per unit rise in pressure: the higher the blood pressure, the lower the slope. Thus essential hypertensive subjects have a smaller decrement in blood volume per unit rise in pressure than normal subjects. 3. The relation between change in blood volume and change in pressure was confirmed in each individual by defining for each a ration deltaV/deltaP, statistically identical with the hyperbolic slope dV/dP. The deltaV/deltaP ratio was found to be well correlated with the renal blood flow and the creatinine clearance. No correlation existed between the total blood volume and these two renal parameters. 4. It is concluded that the present study demonstrates a blood volume regulation disturbance in essential hypertension and provides evidence from human studies that a renal defect accompanies high blood pressure.

Simultaneous determinations of cardiac output and brachial arterial blood flow were performed in patients with hypertension and high cardiac output in comparison with normal subjects of the same age. Brachial arterial blood flow was measured with a previously described pulsed Doppler apparatus that permitted the noninvasive determination of arterial diameter and blood flow velocity. In patients with borderline hypertension, brachial blood flow was significantly increased (136 +/- 11 vs 72 +/- 8 ml/min; p less than .001). After short-term administration of indomethacin, cardiac output decreased while brachial blood flow remained constant. After short-term administration of a selective beta 1-receptor antagonist (primidolol) and nonselective blocker (propranolol), cardiac output decreased significantly in both cases but the decrease in brachial blood flow was significant only after the administration of the nonselective beta-blocking agent. The study strongly suggested that in patients with borderline hypertension, the increased cardiac output is related to a prostaglandin and beta 1-adrenergic mechanisms whereas the increased brachial blood flow depends mainly on beta 2-adrenergic mechanisms.