摘要:

2-adrenergic receptors, increased levels of a^-adrenergic receptors are present in primary Raynaud's disease, and patients show an increased sensitivity to a^-adrenergic receptor agonists on finger blood flow. Serotonin has also been implicated, but the evidence is not compelling. In secondary Raynaud's phenomenon, vasospastic attacks can often be explained by a low arterial distending pressure, a thickened vessel wall, or absence of /J-adrenergic receptor activity. Diagnosis of primary Raynaud's disease relies on a typical history and normal physical examination, laboratory studies, and nailfold capillaroscopy. Finger systolic blood pressures during local cooling with ischemia may be helpful to document vasospastic attacks but does not distinguish primary from secondary Raynaud's phenomenon. The treatment of Raynaud's phenomenon is usually conservative. Pavlovian conditioning or biofeedback may be beneficial. When drug therapy is necessary, the calcium channel entry blocker nifedipine or sympatholytic agents have been shown to decrease the frequency and duration of vasospastic attacks in about two thirds of patients, although subjective improvement does not usually correlate with objective testing. Direct-acting vasodilators have not been shown to be of definite benefit New therapies include prostaglandins, captopril, and the serotonergic antagonist ketanserin. Surgical sympathectomy has not been beneficial.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

-4-carboxyphenyl jV,iV-diphenylcarbamate) attenuated contractions to norepinephrine but not those to caffeine. The augmented response to norepinephrine in hypertensive rats did not occur early after implantation of the mineralocorticoid, suggesting that this vascular change may not play a role in the development of high blood pressure in this experimental model. The augmented response to norepinephrine was reduced in mineralocorticoid-treated rats maintained on a low sodium diet, and these rats had blood pressures in the normotensive range. Because contractile responses to caffeine were not enhanced in arteries from hypertensive rats, we conclude that the cellular store for calcium is not enlarged compared with that in normotensive arteries. In contrast, the mobilization of calcium from cellular stores by norepinephrine is augmented in mineralocorticoid hypertension. This augmented response may be linked to altered phospholipase C activity and thus to an augmented action of inositol trisphosphate that releases calcium from intracellular sites.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 /tm) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3xlO~7 M) dilated pial arterioles by 35±6% (mean±SEM) in WKY rats, but only 21±3% in SHRSP (p<0.05 versus WKY rats). Both nitric oxide (5 x 10~7 M) and nitroglycerin (10"′ M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10~5 M) produced more vasodilatation in WKY rats than in SHRSP (32±8% versus 9±4%, p<0.05). Responses to A23187 (10* M) were inhibited by indomethacin (46±13% versus 15±5%, p<0.05) in WKY rats, whereas responses to A23187 (10"′ M) were potentiated modestly by indomethacin (-3±2% versus 4±2%, p<0.05) in SHRSP. Thus, 1) chronic hypertension impairs responses to two distinct endotheliumdependent dilators in pial arterioles, 2) responses of pial arterioles to nitric oxide are not altered during chronic hypertension, 3) impairment of endothelium-dependent responses in chronic hypertension involves an alteration in postreceptor mechanisms, and 4) impaired responses to A23187 in chronic hypertension may be due in part to co-release of a constrictor substance through the cyclooxygenase pathway.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Inhibition of active sodium transport by ouabain was found to cause concentration- and time-dependent impairment of acetylcholine-induced relaxation in human resistance arteries with a significant effect at 100 pM. The reduced acetylcholine response was attributable to inhibition of the A^-monomethyl L-argjnine-sensItive but not the indomethacin-sensitive component of relaxation. Relaxation by sodium nitroprusside was not affected by ouabain, suggesting that inhibition of sodium transport, directly or indirectly, must affect synthesis or release of endothelium-derived relaxing factor rather than its effector pathway. These results do not support the existence of an additional endothelium-derived relaxing factor other than endothelium- derived relaxing factor, which is dependent on sodium pump activity. The finding that inhibition of sodium transport has a profound effect on vascular relaxation may have implications in the pathogenesis of certain forms of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Angiotensin II, when given in low doses, raises blood pressure slowly. When tested in vitro on vascular smooth muscle cells, it has mitogenic and trophic effects; it is not known if it has these effects in vivo. Our purpose was to determine whether vascular hypertrophy develops during slow pressor infusion of angiotensin II and, if so, whether it is pressure induced. Three experiments were done in rats infused subcutaneously with angiotensin II (200 ng/kg/min) by minipump for 10-12 days. Experiment 1: Angiotensin II gradually raised systolic blood pressure (measured in the tail) from 143±2 to 208±8 mm Hg (mean±SEM), significantly suppressing plasma renin and increasing threefold (NS) plasma angiotensin II. There was no loss of peptide in the pump infusate when tested at the end of the experiment. Experiment 2: In the perfused mesenteric circulation, vasoconstrictor responses to norepinephrine, vasopressin, and KC1 were enhanced in rats given a slow pressor infusion of angiotensin II, but sensitivity of responses was not altered. This combination of changes suggests that vascular hypertrophy develops during slow pressor infusion of angiotensin II. Experiment 3: Vessel myography was done after angiotensin II infusion with and without a pressor response. Angiotensin II raised systolic blood pressure, increased heart weight, and produced myographic changes of vascular hypertrophy in the mesenteric circulation, increasing media width, media cross-sectional area, and media/lumen ratio. Hydralazine given with angiotensin II prevented the rise of pressure and the cardiac effect but not the vascular changes. Two-way analysis of variance showed that angiotensin II significantly increased media width, media cross-sectional area, and media/lumen ratio, all independent of hydralazine. Thus, although hydralazine inhibits the pressor and cardiac effects of angiotensin II, suggesting a pressor mechanism for the cardiac change, it does not inhibit structural vascular change, which suggests that at least part of the effect has a non-pressor mechanism.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This multicenter, dose-ranging study evaluated the antihypertensive effectiveness of once-daily administration of fosinopril sodium in 220 patients with supine diastolic blood pressure of 95-115 mm Hg. After a 4-week placebo period, patients were randomly assigned to double-blind therapy with either placebo or 10, 40, or 80 mg fosinopril once daily for 4 weeks. If treatment goals were not met, chlorthalidone 25 mg/day was added for weeks 5 to 8. Thereafter, patients could enter the long-term, open-label phase and receive 10-80 mg/day fosinopril plus chlorthalidone, if needed. After 4 weeks of monotherapy, the average decreases in supine diastolic blood pressure were 9% (10 mg), 11.5% (40 mg), and 12.5% (80 mg) compared with 6% in the placebo group. After 8 weeks, the average decreases, with or without diuretic therapy, were 12.5-18.2%, compared with 10.8% with placebo. Blood pressure continued to be well controlled, and the patients showed no evidence of tachyphylaxis or tolerance through 12-15 months of treatment Fosinopril was well tolerated. During the short-term phase, no patient withdrew because of adverse events possibly related to fosinopril; during the long-term phase, nine of 148 patients (6.1%) withdrew for that reason. In patients with mild-to-moderate hypertension, once-daily fosinopril (40 and 80 mg) provided significant antihypertensive effects with or without diuretic therapy. The 10 mg dose was effective in some patients and may be considered a starting dose.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Whole body clearance of atrial natriuretic factor is due to both receptor uptake and enzymatic degradation initiated by neutral endopeptidase 24.11. The effects of neutral endopeptidase inhibition have been studied in seven sodium-replete sheep using SCH 39370, a specific and potent inhibitor of neutral endopeptidase, in the presence or absence of exogenous hormone [rat ANF-(101-126), 2.4 pmol/kg/min for 2 hours]. SCH 39370 alone (2.5 mg/kg bolus) increased plasma atrial natriuretic factor and plasma cyclic GMP levels, lowered arterial pressure for periods beyond changes in plasma atrial natriuretic factor or cyclic GMP, and suppressed both plasma aldosterone and cortisol levels when compared with vehicle injections. The effects of SCH 39370 were similar to or exceeded those of atrial natriuretic factor infusions, which induced significantly greater increases in plasma atrial natriuretic factor (p-0.0l). Neither agent alone was natriuretic When SCH 39370 and atrial natriuretic factor were given together, plasma cyclic GMP but not atrial natriuretic factor levels were increased (/*=0.013) compared with atrial natriuretic factor infusion alone, and the half-life was prolonged (p=0.002) in the presence of SCH 39370. The hypotensive response was greater than that induced by atrial natriuretic factor alone (/?=0.03) but not different from SCH 39370 alone. Inhibitory effects of SCH 39370 on aldosterone levels were similar in the presence or absence of exogenous atrial natriuretic factor. Although not excluding actions of neutral endopeptidase inhibitors mediated by non-atrial natriuretic factor pathways, these results are consistent with a prolonged effect of neutral endopeptidase inhibition to increase tissue atrial natriuretic factor activity and provide further evidence of the importance of neutral endopeptidase in atrial natriuretic factor physiology.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Human essential hypertension has more than one cause, but to dissect out subtypes, markers are required. The maximal activity of red blood cell lithium-sodium countertransport has been shown to be increased in hypertensive patients in case-control and population-based studies; in the latter, its distribution is a mixture of two overlapping but distinguishable subpopulations. In the present study, we classified 705 participants in the Tecumseh Blood Pressure Study as having either normal (mean, 0.234 mmol/1 cells/hr; n=614) or high (mean, 0.463 mmol/1 cells/hr, n=91) red blood cell lithium-sodium countertransport to determine if the red blood cell marker is associated with distinctive physiological characteristics. We found that subjects with elevated lithium-sodium countertransport have higher average blood pressure and a greater prevalence of hypertension than those with normal countertransport and that elevated blood pressure had been present since youth. Hemodynamically, the high countertransport group is characterized by elevated vascular resistance, whereas sympathetic nervous system activity appears to be slightly depressed. Subjects with increased lithium-sodium countertransport, compared with those with normal countertransport, have significantly lower average left ventricular mass index and only very infrequently demonstrate left ventricular hypertrophy. Our results support the usefulness of measurements of the maximal activity of red blood cell lithium-sodium countertransport as a way of distinguishing subgroups in the population. Our data are consistent with the idea that subjects with an elevated maximal activity for red blood cell lithium-sodium countertransport are a subset of the population with a genetic lesion that predisposes them to the development of essential hypertension. (Hypertension 1991; 17:)

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Left ventricular function was studied in young men with a positive family history of hypertension for two generations (n= 15). The findings were compared with three control groups: one age-, sex-, and weight-matched group with a negative family history of hypertension (n=14); one normotensive control group unselected as regards family history of hypertension (n=27); and one group also unselected regarding family history of hypertension but selected with blood pressure criteria to have mild blood pressure elevation (n=59). The group with a positive family history of hypertension, in comparison with the normotensive control group, was heavier, had higher blood pressure, increased left ventricular wall thickness, increased left ventricular mass, and signs of changes in diastolic and systolic left ventricular function. There were no differences in these variables between the group with a positive family history and the other two control groups. Data clearly indicated that subjects with a positive family history of hypertension, as well as subjects with mild blood pressure elevation, were heavier than the normotensive control group. It is not possible to judge, with available data, if the changes in left ventricular morphology and function in the two groups with a different family history of hypertension and in the group with mild blood pressure elevation occurred as a physiological response to the increase in afterload or if the neurohormonal and metabolic disturbances leading to the condition of slight overweight also affected left ventricular function.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

=0.0063) than the mean urinary norepinephrine excretion in normal subjects. These relations were demonstrated to be independent of age, smoking status, and physical activity. Our results are consistent with the hypothesis that insulin mediates sympathetic stimulation in response to dietary intake and increases sympathetic nervous system activity in the obese.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID