摘要:

Nitric oxide first captured the interest of biologists when this inorganic molecule was found to activate cytosolic guanylate cyclase and stimulate cyclic guanosine monophosphate (GMP) formation in mammalian cells. Further studies led to the finding that nitric oxide causes vascular smooth muscle relaxation and inhibition of platelet aggregation by mechanisms involving cyclic GMP and that several clinically used nitrovasodilators owe their biological actions to nitric oxide. Nitric oxide possesses physicochemical and pharmacological properties that make it an ideal candidate for a short-term regulator or modulator of vascular smooth muscle tone and platelet function. Nitric oxide is synthesized by various mammalian tissues including vascular endothelium, macrophages, neutrophils, hepatic Kupffer cells, adrenal tissue, cerebellum, and other tissues. Nitric oxide is synthesized from endogenous L-arginine by a nitric oxide synthase system that possesses different cofactor requirements in different cell types. The nitric oxide formed diffuses out of its cells of origin and into nearby target cells, where it binds to the heme group of cytosolic guanylate cyclase and thereby causes enzyme activation. This interaction represents a novel and widespread signal transduction mechanism that links extracellular stimuli to the biosynthesis of cyclic GMP in nearby target cells. The small molecular size and Iipophilic nature of nitric oxide enable communication with nearby cells containing cytosolic guanylate cyclase. The extent of transcellular communication is limited by the short half-life of nitric oxide, thereby ensuring a localized response. Labile nitric oxide-generating molecules such as 5-nitrosothiols may be involved as precursors or effectors. Further research will provide a deeper understanding of the biology of nitric oxide and the nature of associated pathophysiological states.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The relation between intra-abdominal visceral fat accumulation and blood pressure was investigated in 67 obese women (mean body mass index, 33.6±3.1; average age, 50±ll years). As an index of intra-abdominal fat accumulation, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area was determined using a computed tomographic section at the level of the umbilicus. When the obese subjects were divided into a hypertensive group and a normotensive group, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area in the hypertensive group was significantly higher (0.53±0.33 versus 0.29±0.12,p< 0.01). Significant correlations between the ratio of intra-abdominal visceral fat area to subcutaneous fat area and systolic blood pressure (r= 0.62,p< 0.001) and diastolic blood pressure (r= 0.53,p< 0.001) also were found. However, no significant difference existed in either the body mass index or the waist-to-hip circumference ratio between the hypertensive and normotensive groups. Plasma renin activity, aldosterone, epinephrine, and norepinephrine levels were not significantly different between the two groups. Moreover, the correlation between the ratio of the intra-abdominal visceral fat area to subcutaneous fat area ratio and blood pressure was found independent of age and body mass index by multiple regression analyses. We conclude that intra-abdominal fat accumulation itself may play an important role in the pathogenesis of hypertension in obesity.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Subjects with a family history of parental hypertension are reported to have a slightly higher office blood pressure in the prehypertensive stage. Whether this reflects a hyperreactivity to blood pressure measurement or a more permanent blood pressure elevation, however, is not known. In the present study, blood pressure was measured in 15 normotensive subjects whose parents are both hypertensive (FH+ +), 15 normotensive subjects with one hypertensive parent (FH+-), and 15 normotensive subjects whose parents are not hypertensive (FH−); among the three groups, subjects were matched for age, sex, and body mass index. The measurements were made in the office during a variety of laboratory stressors and during a prolonged resting period, and for a 24-hour period (ambulatory blood pressure monitoring). Office blood pressure was higher in the FH++ group than in the FH− group (p< 0.05). The pressor responses to laboratory stressors were similar in the two groups, but the FH++ group had higher prolonged resting and 24-hour blood pressure than the F H− group; the difference was always significant (p< 0.05) for systolic blood pressure. The FH++ group also had a greater left ventricular mass index (on echocardiographic examination) than the FH− group (p< 0.01). The blood pressure values and echocardiographic values of the FH+− group tended to be between those of the other two groups. Thus, the higher blood pressure shown by individuals in the prehypertensive stage with a family history of parental hypertension does not reflect a hyperreactivity to stress but an early permanent blood pressure elevation. Because blood pressure is related to cardiovascular disease even within the normotensive range, we can speculate that these individuals are at increased risk even before hypertension develops.

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

摘要:

The relations of systolic and diastolic blood pressures to alcohol intake and exercise tolerance levels in 15,612 men and 3,855 women were investigated. Alcohol intake was assessed by questionnaire and stratified into seven levels for men and six for women according to the ounces of ethanol consumed per week. Exercise tolerance was determined by maximal treadmill exercise testing and was categorized into six age-specific by sex-specific levels. Both systolic and diastolic blood pressure were significantly related to both alcohol intake and exercise tolerance levels in both men and women. These relations, which were positive for alcohol and negative for exercise tolerance, remained after covariance adjustment for age, body mass index, and cigarette smoking. Alcohol intake was not significantly correlated with exercise tolerance. The relation of blood pressure to alcohol was not linear because the blood pressure of moderate consumers of alcohol tended to be slightly lower than that of nondrinkers. Higher blood pressure was found only in drinkers whose ethanol intake exceeded 9.5 ounces (∼285 ml or 19 drinks) per week. However, heavy drinkers in high exercise tolerance categories had no higher blood pressure than nondrinkers in low exercise tolerance groups. Exercise tolerance or physiological fitness appears to be important in quantifying the relation between alcohol intake and blood pressure and should be considered in describing this relation.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The present study was designed to investigate the role of abnormalities in red blood cell sodium-potassium-chloride (Na-K-Cl) cotransport and Na+ pump as predictors of the pressor response to chronic oral Na+ loading in young whites and blacks. Subjects were healthy adults from 18 to 23 years of age and included normotensive whites (n= 24) and normotensive blacks (n= 35). Red blood cell transport studies were performed before Na+ loading. The Na+ load consisted of 10 g NaCl daily added to the usual diet A sodium-sensitive response was denned as an increase of 5 mm Hg or more in mean arterial pressure after the Na+ load; a sodium-insensitive response was a less than 5 mm Hg increase in mean arterial pressure. A sodium-sensitive response occurred in 16% of whites and 57% of blacks. Black subjects have a significantly lower (p< 0.005) maximal rate of furosemide-sensitive Na+ efflux and a higher Kmfor cellular Na+ (p< 0.05) to activate Na-K-Cl cotransport than white subjects. Normotensive blacks with sodium-sensitive blood pressure response had a higher Km(14.4±6 mmol/1 cell,n= 17, mean±SD) to activate the cotransport than sodium-insensitive blacks (9.9±3.7 mmol/1 cell,n= 13,p< 0.001). Normotensive whites had a significantly lower red blood cell Na+ content (p< 0.05) and a higher maximal rate of cotransport (p< 0.005) than young normotensive blacks. The four young whites with a sodium-sensitive blood pressure response had a significantly lower maximal rate of the cotransport than the sodium-insensitive subjects. The maximal rate of ouabain-sensitive Na+ efflux was similar in blacks and whites and in sodium-sensitive and sodium-insensitive subjects, but it displayed significant sex differences in all groups. These results indicate that a high Kmof the Na-K-Cl cotransport is a predictor of a sodium-sensitive blood pressure in normotensive young blacks.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Plasma ionized calcium, platelet cytosolic calcium (using the fura-2 method in gel-filtered platelets), parathyroid hormone (both the intact hormone and a midmolecule portion), calcitriol, and calcidiol were measured in 19 untreated male patients with essential hypertension and 19 age-matched normotensive male research subjects. Mean levels of platelet cytosolic calcium, parathyroid hormone, calcitriol, and calcidiol were all significantly higher, whereas plasma ionized calcium was significantly lower, in the hypertensive group compared with the normotensive group. Both platelet cytosolic calcium and intact parathryoid hormone were positively correlated with mean arterial pressure (r= 0.58,p< 0.001;r= 0.S4,p< 0.001, respectively), whereas plasma ionized calcium was inversely correlated with mean arterial pressure (r= − 0.60,p< 0.001) in the combined group of all study subjects. All three of these correlations were significant in the hypertensive group alone but not in the normotensive group alone. When analyzed with plasma ionized calcium, body mass index, serum calcitriol, and calcidiol in a multivariable regression model, the significance of the partial regressions of platelet cytosolic calcium and parathyroid hormone with mean arterial pressure persisted. Intact parathryoid hormone was positively correlated to platelet cytosolic calcium (r= 0.43,p< 0.01) and plasma ionized calcium was inversely correlated to platelet cytosolic calcium (r= −0.44,p< 0.01). These results confirm previous reports of disturbances of calcium metabolism in essential hypertension and suggest that the elevated platelet cytosolic calcium observed in essential hypertension may be linked to one or more of these alterations of calcium metabolism.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The hypothesis that 1,25-dihydroxyvitamin D3[l,25-(OH)2vitamin D3] modulates vascular smooth muscle contractile function was tested. 1,25-(OH)2vitamin D3(50 ng/day) was administered by intraperitoneal injection over a 3-day period to 13–15-week-old male spontaneously hypertensive and Wistar-Kyoto normotensive rats. On the fourth day, serum was prepared and contractile force generation of isolated mesenteric resistance arteries was examined. Treatment with 1,25-(OH)2vitamin D3approximately doubled serum levels of the hormone and increased ionized and total serum Ca2+and phosphate by 5–10%. No effect on blood pressure was detected. 1,25-(OH)2vitamin D3injection in both strains enhanced maximal stress generation to norepinephrine and serotonin by 30–40%, with no effect on apparent sensitivity of the vessels to the agonists. To assess the effect of a maneuver that elevates serum ionized Ca2+without the addition of exogenous hormone, maximal stress generation was examined in resistance arteries isolated from rats fed diets containing 0.5% or 2% calcium over a 6–7-week period. Maximal stress generation in response to norepinephrine was greater in vessels from rats of both strains maintained on 0.5% calcium. It is concluded that 72-hour in vivo treatment with 1,25-(OH)2vitamin D3increases contractile force-generating capacity of resistance arteries without affecting blood pressure. It is proposed that this action of 1,25-(OH)2vitamin D3is the result of a direct action of the hormone on the vascular wall.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The function of the endothelium is impaired in hypertension. In spontaneously hypertensive rats (SHR), acetylcholine-induced relaxation is decreased and serotonin-induced constriction is increased. The goal of our study was to evaluate the effect of a long-term treatment with cilazapril, a new angiotensin converting enzyme inhibitor, or hydralazine, a vasodilator, on the endothelium-dependent responses in aorta of SHR. Wistar-Kyoto rats were used as normotensive reference. Isolated aortic rings with or without endothelium were suspended in organ chambers. The rings with intact endothelium were contracted with norepinephrine. Acetylcholine- induced relaxation was markedly enhanced by cilazapril treatment The tension achieved at maximal relaxation was 8 ±4% of norepinephrine contraction in the cilazapril-treated SHR versus 55±5% in the untreated SHR (p< 0.001). Hydralazine had no significant effect The effect of serotonin was also markedly modified by cilazapril. In untreated SHR, serotonin induced the release of a vasoconstrictor substance by the endothelium as assessed by the ratio of maximal tension induced by serotonin in rings with endothelium over maximal tension in rings without endothelium, which was greater than 1. This ratio was reversed in cilazapriltreated SHR but not in hydralazine-treated SHR. Captopril had effects similar to cilazapril. Finally, evaluation of carotid arteries showed that cilazapril also prevented morphological changes of the intima in SHR (i.e., infiltration by mononuclear cells). We conclude that angiotensin converting enzyme inhibitors prevent the functional and morphological alterations in endothelium that are found in hypertension and speculate that this action might participate in their antihypertensive effect

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