ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of S2-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S2-serotoniiiergic antagonist with additional α1-adrenergic blockmg properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes In cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either α1-adrenergic biockers or diuretics. Several studies have shown a greater efficacy in older (> 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S2-serotoninergic or α1-adrenergic blockade alone, but an interaction between the two effects appears to be required.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We performed simultaneous noninvasive measurements of common carotid artery and brachial artery hemodynamics in nine normal subjects and 10 subjects with sustained essential hypertension. In hypertensive subjects, brachial artery blood flow and forearm vascular resistance were in the normal range while carotid artery blood flow and carotid artery resistance were decreased and increased, respectively. The most important findings were the changes in the internal caliber of large arteries. Although the brachial and carotid artery diameters of hypertensive subjects were measured for the same level of mean arterial pressure, brachial artery diameter was significantly increased and carotid artery diameter was strictly normal as compared with values found in normal subjects. To assess whether carotid artery circulation could influence the baroreceptor reflex response to arteriolar vasodilation, carotid artery and brachial artery hemodynamics were measured in immediate succession in normotensive and hypertensive subjects before and after oral administration of cadralazine, a dihydralazine derivative. After cadralazine treatment, carotid artery tangential tension decreased in hypertensive subjects, and the changes were significantly correlated to the Increase in heart rate. A similar correlation was found in normal subjects, but it was reset toward higher heart rates. These results indicate that the carotid artery does not behave like the brachial artery in response to a chronic increase in blood pressure. This behavior indicates intrinsic alterations of the arterial wall and might be involved in the resetting of the carotid baroreceptor reflex. Carotid artery circulation could play a role in hypertension by modulating the carotid baroreceptor mechanisms involved in the response to drug-induced arteriolar vasodilation. Whether these findings represent a primary or a secondary event remains to be determined.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Primary aldosteronism is an uncommon cause of hypertension but one of particular interest because of its distinctive pathophysiological mechanism of blood pressure elevation. Aldosterone has been associated with increased Na+, K+-adenosine triphosphatase (ATPase) activity, but there is controversy over which sodium transport parameters are responsible for this increase. We measured intracellular sodium, ouabain-sensitive and ouabain-insensitive sodium efflux, and the number of Na+, K+-ATPase sites of washed erythrocytes, as well as Na+-Li+ countertransport and the Li++-K+ cotransport rate constant of lithium-loaded red blood cells (RBCs) in six patients with primary aldosteronism and in 50 normal subjects. Ouabain-sensitive sodium efflux was significantly (p< 0.001) higher for the primary aldosteronism patients than for normal subjects (1.85 ± 0.29 vs 1.51 ± 0.21 mmol/L RBC/hr) even though the intracellular sodium concentration (7.2 ± 1.5 vs 6.7 ± 1.9 mM) and the number of the Na+, K+-ATPase sites per RBC (331 ± 52 vs 385 ± 97) were not increased. The elevated sodium efflux appeared to be due to a significant (p< 0.001) increase in the rate constant (1.60 ± 0.12 × 10−15vs 1.28 ± 0.15 × 10−15mmol/site/hr) of the ouabain-sensitive sodium efflux. The rate constant decreased significantly (p< 0.01) after treatment.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We have previously reported that captopril stimulates thromboxane A2synthesis in patients with essential hypertension. In the present study, the hypotensive effects of captopril and OKY-046, a selective inhibitor of thromboxane A2synthetase, were studied in nine patients with essential hypertension to determine whether thromboxane A3 is involved in the regulation of blood pressure. A single oral dose of OKY-046 (400 mg) decreased urinary thromboxane B2(a stable metabolite of thromboxane A]) excretion significantly (from 113 ± 19.0 to 51.0 ± 6.1 pg/min;p< 0.01) and increased urinary sodium excretion significantly (from 73.0 ± 15.3 to 113.0 ± 14.4 μ.Eq/min;p< 0.01), but no change was observed in mean arterial pressure. The administration of OKY-046 (600 mg/day) for 3 days induced a significant and sustained decrease in urinary thromboxane B2excretion, but it did not affect the mean arterial pressure. Although captopril (50 mg) alone induced a significant increase in urinary thromboxane B2excretion (from 91.4 ± 11.0 to 297.3 ± 30.8 pg/min;p< 0.001) and a significant decrease in mean arterial pressure (from 97.0 ± 4.7 to 88.1 ± 5.1 mm Hg;p< 0.01), captopril in combination with OKY-046 induced a decrease both in urinary thromboxane B2excretion (from 70.8 ± 12.3 to 54.2 ± 14.7 pg/min;p< 0.01) and in mean arterial pressure (from 105.1 ± 3.8 to 84.2 ± 3.6 mm Hg;p< 0.01). Thus, the hypotensive effect of captopril was potentiated by OKY-046. OKY-046 did not affect the changes in plasma renin activity and plasma aldosterone concentration and blunted urinary prostaglandin E2and 6-keto-prostaglandin F, a excretion in response to captopril. These results indicate that thromboxane A2counteracts the hypotensive effect of captopril in patients with essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

In a double-blind, within-patient study, blood pressure was measured at regular intervals at the clinic by the physician and each day at home by the patient. Both methods of blood pressure measurement demonstrated an antihypertensive effect of the diuretics chlorthalidone (25 mg) and triamterene (50 mg) and the β-blocker oxprenolol (160 mg) and the greater efficacy of the combination of the two therapies. During placebo, as well as during active treatment, blood pressure values were higher at the clinic than at home, except when the patients were taking the β-blocker, which minimized the arousal response during blood pressure measurements in the clinic. With 2-week treatment periods, separated by 2 weeks of placebo administration, blood pressure returned toward its initial level after each of the three treatments and none of the carryover effects was significant at the 5% level. This methodology was intended to make it possible to demonstrate in 27 patients at the clinic and in 20 patients with measurements made at home, at the usual statistical risks (α=5%, β=10%), a fall of 5 mm Hg in diastolic blood pressure in comparison with a placebo. Moreover, at the end of this 3-month follow-up, each patient could continue to receive the treatment that was the most effective and the best tolerated. In conclusion, the use of a within-patient trial design, with a 15-day washout period between active treatments and careful recording of blood pressure values, can minimize the number of patients included in hypertension trials and offer to each patient the possibility of individualization of treatment.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We studied the effect of converting enzyme inhibition with enalapril on the natriuresis observed after administration of atrial natriuretic factor (human ANF-99–126], given as a 100-fig bolus i.v. injection) in eight healthy humans consuming a 100 mmol sodium diet. Without enalapril, sodium excretion rose from 127 ± 19 (mean ± SE) to 437 ± 103 μmol/min in the first 20 minutes after ANF was administered. Clearance studies performed during maximal water diuresis indicated a rise in glomerular filtration rate (inulin clearance), free water clearance, phosphate, lithium, uric acid, and magnesium excretion. Four days of enalapril (20 mg b.i.d.) increased effective renal plasma flow (p-aminohippurate clearance) and reduced blood pressure (from 114/71 ± 2/2 to 105/60 ± 2/1 mm Hg). Under these conditions baseline sodium excretion was not different from the control study, but it rose less after ANF (from 117 ± 22 to 242 ± 63 μmol/min), and the increments in glomerular nitration rate, free water clearance, phosphate, lithium, uric add, and magnesium were all blunted and nonsignificant. In addition, effective renal plasma flow tended to fall; this effect was not observed when ANF was given without enalapril. These results support the notion that the effects of ANF on renal hemodynamics and on tubular sodium handling depend on renal angiotensln II and that blood pressure reduction may interfere with the ANF-induced natriuresis.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

This study was designed to assess whether the acute blood pressure response of an individual hypertensive patient to a calcium antagonist or an angiotensin converting enzyme (ACE) inhibitor is a good predictor of the long-term efficacy of these drug classes in this particular patient. The concept that good responses to ACE inhibitors and calcium antagonists may be mutually exclusive was also tested. Sixteen patients were included in a randomized crossover trial of enalapril, 20 mg daily, and diltiazem, 120 mg daily, for 6 weeks each. Blood pressure was measured by ambulatory blood pressure recording. During the washout phase, the acute effect of nifedlpine, 10 mg p.o., and enalaprilat, 5 mg i.v., was evaluated. Nifedipine and enalaprilat reduced blood pressure equally well. The long-term blood pressure reduction induced by enalapril and diltiazem was similar. The acute blood pressure response to a given drug was not a good predictor of the result obtained with long-term therapy. No age dependency of the antihypertensive effect of either drug class was apparent. There was no evidence that a good response to one drug excluded a similarly good response to the other.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The effect of selective glucocorticoid or mineralocorticoid replacement on pressor responses to angiotensin I and II and norepinephrine was studied in adrenaiectomized rats given high salt intake. Four groups were prepared by 1) adrenalectomy only (n=5); 2) adrenalectomy plus aldosterone, 6 μg/24 hr i.p. (n=5); or 3) adrenalectomy plus dexamethasone, 10 μg/24 hr i.p. (n=5), using miniosmotk pumps; and 4) sham adrenalectomy (controls; n=5). Plasma corticosterone was undetectable in all three adrenaiectomized groups. Plasma aldosterone concentration was similar in aldosterone-replaced and sham-operated controls. Pressor responses to various doses of angiotensin I, angiotensin H, and norepinephrine were determined in unanesthetized, undisturbed rats. Compared with both control and dexamethasone-replaced rats, pressor responses to all three agonists were significantly reduced in both nonreplaced adrenaiectomized and aldosterone-replaced groups. Comparing the ratios of the pressor responses to angiotensin I and angiotensin II in the four groups over the entire dose range suggests that a greater fraction of injected angiotensin I was converted to angiotensin II in nonreplaced adrenaiectomized rats than in the other three groups. We conclude that glucocorticoid action markedly contributes to the systemic pressor effect of angiotensin and norepinephrine. However, glucocorticoid deficiency does not impair in vivo conversion of angiotensin I to angiotensin H.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Isolated kidneys of Dahl salt-sensitive rats (DS) excrete sodium less readily than those of Dahl salt-resistant rats (DR). The collecting tubule is an important source of papillary prostaglandin E2and is a site of significant sodium reabsorption. We cultured renal papillary collecting tubule cells from 5-week-old, prehypertensive DS and DR on a low salt diet and also after 14 weeks of high salt feeding, and we measured prostaglandin E2synthetic capacity. Unstimulated renal papillary collecting tubule cells from 5-week-old DS produced 62 ± 5% less prostaglandin E2than did comparable cells from DR (p< 0.001). The cells from DS also synthesized less prostaglandin E? after stimulation with the calcium ionophore A23187 (67 ± 6% of control; p < 0.001) or the addition of exogenous arachidonate (74 ± 7% of control;p< 0.01). Urinary prostaglandin E? excretion was also diminished in the 5-week-old DS compared with their salt-resistant counterparts (18.1 ± 1.3 vs 23.9 ± 1.7 ng/24 hr;p< 0.025). After high salt feeding, the DS became hypertensive but the DR remained normotensive. Renal papillary collecting tubule cells cultured from these DS continued to produce less prostaglandin E2than those from control rats, both in the basal state (60 ± 12% of control;p< 0.09) and after stimulation with ionophore (62 ± 2% of control;p< 0.002). In these older animals, the DS continued to underexcrete prostaglandin E? compared with the DR (29.7 ± 3.2 vs 42.2 ± 6.1 ng/24 hr;p< 0.08). The underproduction of prostaglandin E2in the papillary collecting tubule of DS may play a role in their inadequate renal natriuretic capacity and contribute to the onset and maintenance of saltinduced hypertension in this strain.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID