摘要:

The effects of diltiazem treatment (40–50 mg/kg/day orally for 8 weeks) of left ventricular hypertrophy on systemic and coronary hemodynamics and mechanical cardiac performance were investigated in renovascular hypertensive rats (Goldblatt, two-kidney, one clip). Systemic and coronary hemodynamics were determined by using radioactive microspheres in conscious, unrestrained rats. Mechanical performance was measured on isolated papillary muscle from the same animal. Nine treated hypertensive rats were compared with control groups: 12 untreated hypertensive and nine sham-operated rats. Diltiazem treatment led to an effective but incomplete control of blood pressure (from 208 ± 5 mm Hg in the untreated hypertensive group to 155 ± 3 mm Hg in the treated hypertensive group; p < 0.01) associated with a significant but incomplete decrease of the left ventricular mass (from 3.10 ± 0.19 mg/g in untreated hypertensive rats to 2.35 ± 0.04 mg/g in treated hypertensive rats; p < 0.01). A close correlation was found between left ventricular mass and systolic blood pressure in untreated, treated, and pooled groups (r=0.84, p < 0.001, n=30). The left ventricular weight to systolic blood pressure ratio was equivalent in all three groups, so that the reduction of left ventricular mass in diltiazem-treated rats was commensurate with the reduction of blood pressure. At rest, treated hypertensive rats showed a rise in cardiac output (426 ± 12 vs 298 ± 22 ml/min/kg in sham-operated rats; p < 0.001) and in coronary blood flow (598 ± 17 vs 453 ± 19 ml/min/100 g; p < 0.05) related to the decrease in total peripheral resistance and in total left ventricular coronary resistance. A reversal of impaired myocardial mechanical parameters toward control values was observed except for time to half-maximal relaxation (92 ± 2 msec in the treated group vs 79 ± 5 msec in sham-operated rats) and time to peak force. Our results demonstrate that even incomplete control of blood pressure with diltiazem is associated with significant but partial reduction of left ventricular mass and improvement of mechanical function.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Since it was previously reported that atrial natriuretic factor (ANF) may exert an inhibitory effect on renin release, the existence of an Angiotensin II (Ang II)-ANF feedback mechanism was investigated. Male rats were infused intraperitoneally for 7 days with either saline, a nonpressor dose of Ang II (200 ng/kg/min), or a pressor dose (800 ng/kg/min) of Ang II. Systolic blood pressure, plasma ANF, 24-hour urinary sodium excretion, urine volume, and water intake were measured. A significant increase in plasma ANF was observed in the group with a pressor response (blood pressure rose from 89.0 ± 3.9 to 136.7 ± 11.4 mm Hg; ANF rose from 36.8 ± 4.9 to 92.7 ± 17.7 pg/ml). There was no significant time effect on 24-hour sodium excretion, urine volume, and water intake in both Ang II-infused groups. In a second set of experiments, male rats were infused intravenously for 60 minutes with either saline, a nonpressor dose of Ang II (16 ng/kg/min), or a pressor dose (800 ng/kg/min) of Ang II. Left ventricular end-diastolic pressure, right atrial pressure, and mean arterial pressure were monitored. There was a significant increase in plasma ANF and left ventricular end-diastolic pressure only with the pressor dose (blood pressure rose from 85.0 ± 6.1 to 140.0 ± 5.5 mm Hg; ANF rose from 22.6 ± 6.0 to 108.3 ± 47.7 pg/ml; left ventricular end-diastolic pressure rose from 5.3 ± 5.7 to 20.8 ± 7.9 mm Hg). No significant modification of right atrial pressure was recorded. In a last set of experiments, atrial slices were incubated for 30 minutes with Ang II in increasing doses from 10−8to 10−5M without any modification in ANF release into the medium. Thus, ANF release induced by pressor doses of Ang II seems to be mediated by hemodynamic changes, particularly by an elevation of left ventricular end-diastolic pressure rather than right atrial pressure.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Experimental and clinical data suggest an association between chronic hyperparathyroidism and hypertension, but acute infusion of parathyroid hormone causes vasodilation and hypotension. These observations imply that chronic and acute parathyroid states affect blood pressure through different mechanism(s), either by modification of vascular receptors or by an ionophoretic effect of parathyroid hormone. The effect of parathyroid status induced by dietary calcium manipulations or by surgical ablation of the parathyroid gland on the hypotensive response of parathyroid hormone infusion was studied in rats. At 4 weeks of age 24 male rats were divided into four equal groups. Three groups were sham-operated, and one group was thyroparathyroidectomized. Only the thyroparathyroidectomized group was treated with thyroxine, 10 μg/kg/day. The control and thyroparathyroidectomized groups were raised on a 1.4% calcium diet; the other two groups were raised on 0.005% and 2.8% calcium diets. After 8 weeks on the diets, parathyroid hormone was infused through a venous cannula at 5 and 10 μg/kg doses and blood pressure was measured through arterial cannulas. The results indicate that hyperparathyroidism and hypocalcemia induced by the low calcium diet attenuated the hypotensive response to parathyroid hormone compared with responses in rats raised on a 1.4% calcium diet. In hypoparathyroid rats (2.8% Ca diet) with hypercalcemia, the hypotensive response was also reduced. However, in hypoparathyroid (thyroparathyroidectomized) rats with hypocalcemia, the hypotensive response was enhanced. The data suggest that chronic parathyroid status, as well as hypercalcemia, alters the hypotensive response to parathyroid hormone infusion, presumably by altering the vascular parathyroid hormone receptors or by some other mechanism.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The vasodilator effect of adenosine on the contraction induced by phenylephrine, an α1 adrenergic receptor agonist, was investigated in the isolated rat aorta. We found that the effect of adenosine was greater in intact aortas than in endothelium-denuded preparations. Denuding caused a parallel shift of the dose-response curve of adenosine to the right by a factor of five in comparison with intact aorta. This finding indicates that the relaxing effect of adenosine is partially endotheliumdependent in rat aorta. The mechanism of action of adenosine on vascular smooth muscle was also investigated in receptor-mediated and voltage-dependent calcium influx experiments performed with the addition of phenylephrine and high potassium concentrations, respectively. Although adenosine significantly inhibited only the tonic phase of the contraction induced by phenylephrine (10−5M), it did so to both the fast and slow phases of the contraction produced by high potassium concentrations (75 mM) with no preferential difference. In comparison to verapamil, a calcium entry blocker, adenosine behaved in a manner similar to that of verapamil in counteracting the constriction induced by either phenylephrine or potassium. We conclude that the vasodilator effect of adenosine is partially endothelium-dependent and that the mechanism of this effect may involve the inhibition of calcium influx and the release of an endothelium-derived relaxing factor.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Alterations in ion transport associated with hypertension have been found in a variety of organs. We used a modified Ussing chamber to compare the NaCl dependence of the short-circuit current across the dorsal lingual epithelium in vitro from spontaneously hypertensive rats (SHR) with that from Wistar-Kyoto rats (WKY). The short-circuit current in response to mucosal NaCl was less in SHR than in WKY at hyperosmotic concentrations (above 0.15 M and up to 2.0 M). Since ion transport in the lingual epithelium has been found to play a role in early events of salt taste transduction, the attenuation in the short-circuit current in hypertensive animals may be a factor in the enhanced salt preference of SHR compared with WKY.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Several experimental forms of hypertension require intact renal innervation for the development or maintenance (or both) of the elevated arterial pressure. We determined the relationships between urinary sodium and water excretion and arterial pressure in Dahl salt-sensitive rats (DS) with innervated (n=6) and denervated (n=7) kidneys after switching from a low to a high sodium diet. Arterial pressure significantly increased in both groups within 48 hours after they began to eat an 8% sodium chloride diet. This hypertension increased to 188 ± 9 and 190 ± 7 mm Hg, respectively, in rats with innervated and denervated kidneys after 12 days. Mean arterial pressures were not significantly different between groups on any day. The rise in arterial pressure of DS placed on a high sodium intake was associated with an elevation of urine flow rate and urinary sodium excretion in rats with either innervated or denervated kidneys. Urine flow rates and urinary sodium excretions were greater in denervated than in innervated rats on Days 4 through 7 after beginning the high sodium diet. This diuresis and natriuresis in rats with denervated kidneys were associated with greater water and sodium intakes on Days 4 to 7 of the high sodium diet when compared with rats with innervated kidneys. These results demonstrate that, following exposure to a high sodium intake, DS have increased arterial pressure within 24 hours. The development of this arterial hypertension is not dependent on intact renal innervation. In conscious DS, the renal innervation does participate in the regulation of urinary sodium excretion by promoting renal sodium and water reabsorption. However, DS with either innervated or denervated kidneys maintained sodium balance and rapidly became hypertensive when fed a high salt diet. Thus, elevation of sodium intake in DS results in arterial hypertension independent of measurable renal neurogenic alterations in salt and water balance.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We studied the effect of high and low NaCI diets in normotensive and borderline hypertensive subjects to determine if a high NaCI diet produces abnormal renal vasoconstriction during the stress of upright posture in borderline hypertensive subjects. We studied 13 normotensive young men with diastolic blood pressures below 85 mm Hg and nine borderline hypertensive young men denned by diastolic blood pressures intermittently above 90 mm Hg. The subjects achieved comparable sodium balance during 6 days of low NaCI (10 mEq Na, 40 mEq Cl, 100 mEq K) and high NaCI (400 mEq Na, 400 mEq Cl, 100 mEq K) diets. In the normotensive subjects, standing for 30 minutes resulted in a tendency for diastolic blood pressure to fall during both diets. In contrast, during standing borderline hypertensive subjects showed no change in diastolic blood pressure during the low salt diet and a tendency for diastolic blood pressure to increase after the high salt diet. Standing reduced renal plasma flow in both groups during both diets. However, only during the high NaCI diet did the absolute decrease and percent decrease in renal plasma flow during standing differ significantly (p< 0.05 andp< 0.01, respectively) between the borderline hypertensive (−151 ± 24 ml/min/1.73 m2; −29 ± 4%) and normotensive subjects (−79 ± 17 ml/min/1.73 m2; −15 ± 3%). The resultant increase in the renal vascular resistance index with standing did not differ between the two groups during the low NaCI diet. In contrast, during the high NaCI diet, standing increased the renal vascular resistance index by 48 ± 12% in borderline hypertensive subjects but only by 14 ± 5% in normotensive subjects (p< 0.01). Standing also reduced free water clearance to a greater extent in the borderline hypertensive subjects compared with normotensive subjects during both diets (low NaCI,p< 0.05; high NaCI,p< 0.01). In summary, dietary NaCI loading in borderline hypertensive subjects produces greater decreases in renal blood flow, enhanced renal vasoconstriction, and enhanced water retention during standing. A high NaCI diet appears to unmask an abnormality in the neurohumoral control of the renal circulation in borderline hypertensive subjects.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We sought to demonstrate a hypotensive effect from infusions of atrial natriuretic factor (ANF) into humans and to describe the mechanism(s) of this effect. Cardiovascular and hormonal responses to human ANF-(99–126) (125 ng/kg bolus followed by a 30-minute infusion at 25 ng/kg/min) were determined in eight conscious volunteers and compared with responses of eight timecontrol subjects who received isotonic saline. Baseline levels of ANF (52.8 ± 5.5 pg/ml) increased 8.8-fold after 30 minutes of ANF infusion but were unchanged in the time controls. Plasma levels of renin, aldosterone, vasopressin, sodium, potassium, and osmolality did not change during infusions. A transient 5% reduction in mean arterial pressure related to a 12% reduction in peripheral resistance was observed 10 minutes after the priming bolus of ANF. This response was not sustained during the remainder of the ANF infusion period, nor did it occur in two additional subjects who received ANF infusions without the priming bolus. Steady state responses consisted of significant reductions in central venous pressure (15%), stroke volume (13%), and cardiac output (10%), but no reduction in blood pressure. Plasma norepinephrine levels and peripheral resistance increased (34% and 9%, respectively) during ANF administration. These data indicate that steady state responses to ANF in humans consist of decreases in cardiac filling pressures, which reduce cardiac output, unload cardiopulmonary baroreceptors, and activate the sympathetic nervous system. Blood pressure is well maintained despite striking increases in plasma ANF.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The reproducibility of ambulatory, home, and clinic blood pressures was compared in 13 untreated mildly hypertensive and 14 normotensive subjects. Each subject had two sets of daily ambulatory recordings, home self-measured readings (over 6 days), and clinic measurements taken 2 weeks apart. Comparisons over the 2 weeks within and among the methods of measurements were made using a repeated-measures analysis of variance. The results showed that there was no consistent average change in the ambulatory or home pressures and no change in clinic diastolic pressures, but the clinic systolic pressure of the hypertensive subjects dropped 6 mm Hg (p< 0.05), while that of the normotensive subjects showed no significant change. Test-retest correlations of each of the three methods were similar in magnitude, indicating a similar level of reliability. Test-retest correlations of the ambulatory standard deviations, however, were low, indicating a low reliability of this measure of daily pressure variability. These results suggest that the reproducibility of ambulatory pressures may be as good or better than that of home or clinic measurements. They also suggest that the average ambulatory pressure may be preferable as the measurement in clinical trials, since it may be less influenced by measurement anxiety, particularly in hypertensive subjects.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The renal and systemic metabolites (the latter as 2,3-dinor derivatives) of prostacyclin and thromboxane A2were measured, along with renal prostaglandin E2and kallikrein, in the urine of 15 patients with pregnancy-induced hypertension, 15 normotensive pregnant women matched for both age and gestational age, and 15 normotensive nonpregnant control women. Urinary excretion of all prostaglandin and thromboxane metabolites studied proved significantly higher in normotensive pregnant women than in controls. Prostaglandin E2, 6-keto-prostaglandin Flcr, and 2,3-dinor-6-ketoprostaglandin F1αwere significantly lower in pregnancy-induced hypertensive women than in normotensive pregnant women, whereas thromboxane B2and 2,3-dinor-thromboxane B2showed no significant differences in the two groups. A significant negative correlation (r=– 0.636,p< 0.01) was found between urinary 2,3-dinor-6-keto-prostaglandin F1αand mean blood pressure in the two groups of pregnant women taken as a whole. These data indicate that, in pregnancy-induced hypertension, there is an imbalance between vasodilator and vasoconstrictor factors, not only in the kidneys, but also at the systemic vascular level. This imbalance, which may in itself produce vasoconstriction, may also potentiate the hypertensive effect of catecholamines and angiotensin II.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID