摘要:

Arterial stiffening is the principal cause of increasing systolic pressure with advancing years and in patients with arterial hypertension. It is associated with progressive arterial dilation and is due to degeneration of the arterial wall, probably as a consequence of repetitive cyclic stress; it increases systolic pressure directly by increasing amplitude of the pressure wave generated by a given flow impulse from the heart and indirectly by increasing wave velocity so that wave reflection from the periphery occurs earlier, augmenting pressure in late systole. The first mechanism affects pressure in both the central and peripheral arteries, the second predominantly in the central arteries. Change in brachial systolic pressure with age underestimates the rise in systolic pressure in the aorta and left ventricle. Arterial stiffness is reduced passively with reduction in arterial pressure. Drugs have little or no direct effect on arterial stiffness but can markedly reduce wave reflection. In patients with stiffened arteries, reduction in wave reflection decreases aortic systolic pressure augmentation. The decreased systolic pressure in central arteries brought about by this mechanism is not detected when systolic pressure is measured in a peripheral (brachial or radial) artery but can be inferred from change in contour of the pressure wave recorded in peripheral arteries.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90–114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25–50 mg) or high (50–100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure <90 and ≤5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/1 occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a double-blind study to receive hydralazine, methyldopa, metoprolol, or reserpine in addition to hydrochlorothiazide; 79.2% responded to the addition of the second drug and 87.3% of these completed a 6-month maintenance phase. Overall, there were no significant efficacy differences among the step 2 regimens. We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose, and the addition of a second drug was effective and generally well tolerated in elderly patients.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We previously described a strong concordance between nocturnal oscillations in plasma renin activity and sleep cycles. To examine whether modifying renal renin content or release influences the response to central stimuli linked to sleep stage alternation, plasma renin activity was measured every 10 minutes from 11:00 PM to 8:00 AM in three groups of six subjects. The first group received one 40 mg dose of the diuretic furosemide; the second group underwent the night experiment after 3 days on a low sodium diet; the third group received one 100 mg dose of the β-blocker atenolol. Each subject underwent a control night when a placebo was given. The nocturnal curves were analyzed with a pulse detection program. For the control nights, 74 of the 83 sleep cycles were associated with significant plasma renin activity oscillations; non–rapid eye movement sleep occurred in the ascending portions and rapid eye movement sleep in the declining portions of the oscillations. These oscillations persisted in the three groups of subjects during the experimental nights and the relation with the sleep stages was not disturbed. Acute stimulation by furosemide amplified the oscillations and led to a general upward trend of the nocturnal profiles. Similarly, a low sodium diet, which led to a slow increase in renal renin content, provoked large oscillations with high initial levels. However, in both cases the mean relative amplitude of the oscillations, expressed as a percentage of the nocturnal means, was similar to that of the control nights and approximated 60%. Atenolol reduced the increases associated with non–rapid eye movement sleep. Small oscillations were detected in 16 of the 23 sleep cycles recorded. These results give evidence of the strength of the sleep-related processes generating the oscillations, which are amplified or depressed by factors known to control renin release. These factors create a baseline environment that modulates the expression of central stimuli associated to the transition from rapid eye movement sleep or waking period toward deep sleep stages.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

To assess the rate of activation of the renin-angiotensin-aldosterone axis and enhancement of adrenal responsiveness to angiotensin II (Ang II) with restriction of sodium intake, 16 healthy male subjects were placed initially on a 200 meq daily sodium intake; adrenal responsiveness to Ang II was assessed, and then daily sodium intake was reduced abruptly to 10 meq. Adrenal responses to Ang II were assessed again during the non–steady state interval 24 and 48 hours later, and after balance was achieved in 5–7 days. Renin-angiotensin system activation was evident within 24 hours after sodium intake was restricted. The increase in basal plasma aldosterone concentration and enhancement of the adrenal response to Ang II, on the other hand, tended to lag. Within 24 hours of restricting sodium intake, despite a significant increase in both plasma renin activity (1.0±0.2 vs. 2.4±0.7 ng/ml/hr,p< 0.01) and Ang II concentration (22.0±1.9 vs. 29.5±1.3 pg/ml,p< 0.05), there was no increase in basal plasma aldosterone concentration (10.4±1.3 vs. 11.7±1.2 ng/dl). At 48 hours, despite little further change in plasma renin activity or plasma Ang II concentration, there was a sharp increase in basal plasma aldosterone concentration (22.5±3.6 ng/dl,p< 0.01). The adrenal response to Ang II was increased significantly at 24 hours, evident at only a 10 ng/kg/min dose, but showed progressive further enhancement with time. Early enhancement was not related to shifts in potassium balance as none occurred, but later progressive enhancement could reflect in part negative potassium balance, as a small but consistent element of negative balance occurred. These observations add further support to the concept that some unidentified factor other than plasma Ang II concentration or potassium balance, but related to sodium balance, modifies the adrenal response to Ang II. Available evidence suggests that enhancement reflects events at the terminal step of aldosterone biosynthesis.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In spontaneously hypertensive rats (SHR), enhanced responsiveness of phospholipase C has been reported in various cells and tissues. In SHR and in some patients with essential hypertension particularly, the increased phospholipase C responsiveness of platelets has been described as involved in the hyperreactivity to thrombin. To determine the relation between such an enzymic abnormality and hypertension, the platelet phospholipase C activity was investigated in various models of experimental hypertension (i.e., in the Dahl salt-resistant and salt-sensitive strains inbred by John Rapp at Toledo, Ohio, SR/Jr and SS/Jr, respectively) fed either on a low or a high NaCl-containing diet, and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In phosphorus-32-prelabeled platelets, phospholipase C was determined by measurement of the thrombin-induced [32P]phosphatidic acid formation; the labeling of the P47 protein with32P was also measured. In parallel experiments, the platelet reactivity was assessed by measurement of the thrombin-induced serotonin release. Under thrombin (0.05–0.5 units/ml) stimulation, phospholipase C activity, [32P]P47 labeling, and serotonin release were significantly increased in SS/Jr rats fed a high NaCl diet compared with SS/Jr rats fed a low NaCl diet. NaCl-rich diet did not modify phospholipase C in SR/Jr rats. Platelet reactivity and phospholipase C responsiveness were also normal in DOCA-salt hypertensive rats compared with controls. These results suggest a lack of relation between phospholipase C activity and high blood pressure; they indicate moreover that the enhanced platelet reactivity and phospholipase C activity observed in SS/Jr rats fed on a high NaCl diet is not secondary to hypertension or to high NaCl intake and is likely of genetic origin, as already observed in SHR. In SS/Jr rats, however, the hyperactivity of the enzyme appears to be NaCl regulated and may be involved in the elevation of blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The capacity of cultured renal medullary interstitial cells derived from Dahl salt-sensitive and salt-resistant rats to synthesize prostaglandin E2(PGE2) was compared. Basal and arginine vasopressin (AVP)-induced PGE2production by interstitial cells from salt-resistant rats was fourfold to fivefold higher than corresponding values of those from the salt-sensitive rats. Similarly, basal and AVP-responsive release of [3H]arachidonate were twofold higher by interstitial cells from salt-resistant compared with salt-sensitive rats. Differences in PGE2production were abolished by the calcium inophore A23187 or the addition of exogenous arachidonate. The latter findings suggested a role for altered availability of endogenous arachidonate, possibly mediated by reduced calcium-responsive lipase activity. Basal and AVP-induced increases in cytosolic free calcium concentration, assessed by the aequorin method, were significantly lower in interstitial cells from salt-sensitive versus salt-resistant rats, further supporting a possible role for altered cellular calcium homeostasis. Studies of the potential contribution of various phospholipases and of triglyceride lipase to the release of arachidonate for PGE2synthesis in interstitial cells implicated phospholipase A2activity as a major pathway. When assessed in vitro in cell cytosolic fractions at identical calcium concentration, phospholipase A2activity was lower in interstitial cells from salt-sensitive versus salt-resistant rats. Thus, both reduced cytosolic free calcium and phospholipase A2activity of interstitial cells from salt-sensitive rats may contribute to the diminished capacity of these cells to liberate endogenous arachidonate for PGE2synthesis.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Cardiovascular dysfunction associated with obesity was assessed by comparing rats that had been maintained on a regular or high fat diet since weaning. Rats on the high fat diet not only gained weight faster than age-matched controls but also had higher systolic and mean pressures. Development of mild hypertension in obese rats was first detected by indirect tail-cuff measurement and confirmed later by recording intra-arterial pressures directly from indwelling femoral catheters. To assess baroreceptor reflex sensitivity, reflex heart rate responses were elicited by lowering blood pressure with sodium nitroprusside or elevating it with phenylephrine. Initial tests showed that, although reflex tachycardia during depressor responses to sodium nitroprusside did not differ between groups, reflex bradycardia during pressor responses to phenylephrine was weaker in obese than in control rats. Underlying autonomic mechanisms were then examined by repetition of baroreceptor reflex tests after cholinergic blockade with methylatropine or β-adrenergic blockade with propranolol. Reflex tachycardia was equally inhibited in both groups by either antagonist. By contrast, reflex bradycardia was reduced more in obese than in control rats by β-adrenergic blockade but was equally reduced by cholinergic blockade. Because residual responses after β-adrenergic blockade would represent remaining parasympathetic mediation, these results indicate that reflex bradycardia was selectively impaired because of deficient parasympathetic mediation. Considered collectively, our results suggest that impaired parasympathetic mediation of reflex bradycardia could either result from or contribute to the blood pressure elevation in obese rats.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg°]Hyp3-Thi5,8[DPhe7] bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32±3 vs. 3±1 mm Hg,p< 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25±4 vs. 26±2 mm Hg; prostaglandin E2, 48±3 vs. 47±8 mm Hg; norepinephrine, 17±2 vs. 18±2 mm Hg; leucine-enkephaline, 15±2 vs. 16±1 mm Hg; neurotensin, 18±2 vs. 19±1 mm Hg; substance P, 19±2 vs. 19±2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44±9 mm Hg (p< 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22±6 mm Hg,p< 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID