摘要:

Hypertension and non-insulin-dependent diabetes mellitus (NIDDM) are characterized by a strong genetic component and impaired ability to store glucose as glycogen in skeletal muscle. Impaired insulin activation and altered genetic control of muscle glycogen synthase, the rate-limiting enzyme for glucose storage in skeletal muscle, could provide an explanation for this insulin resistance. We examined whether there is an association between the glycogen synthase gene (Xba I polymorphism) and hypertension in 304 nondiabetic subjects. We examined glucose tolerance with an oral glucose tolerance test and glucose storage in skeletal muscle with the euglycemic insulin clamp technique in combination with indirect calorimetry. The Xba I A2allele of the glycogen synthase gene was enriched in subjects with hypertension and a family history of NIDDM (48%) compared with normotensive subjects without a family history of NIDDM (6%, P < .0001). The presence of the A2versus the A1allele was associated with decreased rates of insulin-stimulated glucose storage in hypertensive subjects (11.2 plus/minus 2.3 versus 16.9 plus/minus 2.6 micro mol/kg lean body mass per minute, P = .029) but not in normotensive subjects (28.0 plus/minus 4.6 versus 29.6 plus/minus 3.7 micro mol/kg lean body mass per minute). In conclusion, Xba I polymorphism of the glycogen synthase gene identifies a subgroup of hypertensive subjects with a family history of NIDDM. The data suggest that a locus in the glycogen synthase gene region on chromosome 19 may serve as a "thrifty gene," increasing susceptibility for insulin resistance when exposed to other environmental or genetic factors. (Hypertension. 1996;27:67-71.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The aim of the present study was to define the effects of angiotensin II (Ang II) and Ang-(1-7) on free cytosolic Sodium+(Sodium+i), intracellular pH (pHi), and the Sodium+-Hydrogen+antiporter in cultured vascular smooth muscle cells from rat aorta. Cells were loaded with either BCECF-AM or SBFI-AM for measurement of pHiand Sodium+i, respectively. Ang II (10 (-6) mol/L) caused a rapid rise in Sodium+ifollowed by a progressive increase that peaked at about 10 minutes (from 11 plus/minus 1.5 to 16 plus/minus 1.5 mmol/L, P < .001), whereas Ang-(1-7) (10-6mol/L) did not affect Sodium+isignificantly (from 11.5 plus/minus 1.1 to 11.8 plus/minus 0.07 mmol/L). The effect of Ang II on Sodium+iwas concentration dependent (Delta Sodium+i, 5.1 plus/minus 0.9, 3.8 plus/minus 0.6, 1.6 plus/minus 0.6, and 0.14 plus/minus 0.18 mmol/L with decreasing concentrations of 10-6, 10-7, 10-8, and 10-9mol/L, respectively). Ang II caused a brief acidification followed by an increase in pHi(from 7.34 plus/minus 0.03 to 7.43 plus/minus 0.03 after 10 minutes, P < .005), and Ang-(1-7) had no significant effect on pHi(from 7.23 plus/minus 0.03 to 7.23 plus/minus 0.03). To investigate whether pHiand Sodium+ichanges induced by Ang II were due to cell Sodium+entry via stimulation of the Sodium+-Hydrogen+antiporter, we pretreated cells with EIPA (25 micro mol/L) or ouabain (2.0 mmol/L). Ang II in the presence of ouabain caused a greater increase than that seen with ouabain alone (Delta Sodium+i, 13 plus/minus 1.5 versus 6.3 plus/minus 1.2 mmol/L, P < .0025). EIPA by itself decreased Sodium+iand pH (i). After EIPA, Ang II failed to increase both Sodium+iand pHi, demonstrating that the Sodium+-Hydrogen+antiporter is responsible for the rises in Sodium+iand pHiduring stimulation with Ang II. To further characterize the mechanism of Ang II action, we exposed cells to an Ang II type 1 receptor antagonist (L-158,809, 10-6 mol/L) or two different type 2 receptor antagonists (PD 123177 and CGP 421112A, 10-6mol/L). L-158,809 completely blocked the rise in pHicaused by Ang II, whereas PD 123177 and CGP 421112A did not. We conclude that Ang II increases both Sodium+iand pHi, and both effects are mediated by stimulation of the Sodium+-Hydrogen+, anti-porter. Ang-(1-7), by contrast, has no significant effect on Sodium+i, pHi, or the Sodium+-Hydrogen+antiporter. Stimulation of this antiporter by Ang II is exerted through the type 1 receptor. (Hypertension. 1996;27:72-78.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The contribution of endogenous kinins to impairment in renal adaptation to a 6-day period of dietary sodium withdrawal associated with treatment with ramipril (5 mg/kg per day) and losartan (30 mg/kg per day) was evaluated by use of concomitant chronic administration of the bradykinin B2-receptorantagonist Hoe 140 (150 or 300 micro gram/kg per day via subcutaneous osmotic pump). A similar level of higher cumulative sodium excretion was observed in ramipril- and losartan-treated rats compared with untreated animals, and the effect of ramipril was not affected by Hoe 140. Similarly, the fall in arterial pressure and the renal vasodilatation associated with ramipril and losartan were not modified by Hoe 140. Glomerular filtration rate (785 plus/minus 73 micro Liter/min per g KW in untreated sodium-depleted rats) decreased to a larger extent in ramipril-treated rats compared with losartan-treated rats (371 plus/minus 78 and 550 plus/minus 55 micro Liter/min per g KW, respectively). Hoe 140 markedly prevented the alteration in glomerular filtration rate associated with ramipril, thus resulting in a final glomerular filtration rate (543 plus/minus 41 micro Liter/min per g Kw) similar to that observed with losartan. These findings demonstrate that despite a lack of influence on arterial pressure and sodium balance, accumulation of kinins markedly contributes to deterioration of the glomerular filtration rate induced by ramipril in sodium-depleted rats. (Hypertension. 1996;27:79-84.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

On the basis of evidence suggesting the activation of the kallikrein-kinin system in steroid-induced hypertension, we considered the possibility that the angiotensin-converting enzyme inhibitor captopril would lower the arterial blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats through kininase II inhibition. In conscious DOCA-salt hypertensive rats with intact kidneys (n = 6) or uninephrectomized rats (n = 5), the short-term administration of captopril (8 mg/kg IV) decreased mean blood pressure from 141 plus/minus 3 to 118 plus/minus 3 mm Hg (P < .05) and from 176 plus/minus 12 to 158 plus/minus 15 mm Hg (P < .05), respectively. The maximal effect of captopril was manifested between 40 and 50 minutes after its administration, and blood pressure remained depressed for at least 2 hours. The bradykinin B2receptor antagonist Hoe 140 (500 micro gram/kg IV) abolished the antihypertensive effect of captopril in the DOCA-salt hypertensive rats, indicating kinin involvement. Losartan, an angiotensin type 1 receptor antagonist, had no effect on blood pressure in another group of DOCA-salt hypertensive rats (n = 9) and did not significantly change the response to captopril. No effect of the angiotensin-converting enzyme inhibitor was seen in normotensive control rats (n = 5), indicating the absence of a nonspecific hypotensive action of the drug. Plasma renin activity was lower in the DOCA-salt hypertensive rats (0.7 plus/minus 0.2 ng angiotensin I/mL per hour, n = 4) than in normotensive control tats (8.8 plus/minus 1.7, n = 4). The involvement of kinins in the antihypertensive effect of captopril in DOCA-salt hypertension supports the contention that the kallikrein-kinin system contributes to blood pressure regulation in this hypertension model. (Hypertension. 1996;27:85-89.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

To investigate the effects of dietary sodium restriction from conception to adulthood on blood pressure and its regulatory mechanisms, male offspring were derived from inbreeding in spontaneously hypertensive rats fed a diet containing sodium of 175 micro mol/g food (control) or 22 micro mol/g (low sodium), which is the least sodium content for normal growth. While urinary sodium excretion was markedly less, the low sodium diet did not inhibit body growth and failed to blunt the development of hypertension. Neither plasma catecholamine concentration nor depressor response to hexamethonium was different between the two groups at any age examined (8, 12, and 20 weeks). Plasma renin concentration was not elevated, whereas urinary excretion of aldosterone was increased at any age in the low sodium group compared with that in the control group. Other sets of rats were fed a diet containing sodium of 175 micro mol/g plus mefruside (a diuretic) of 0.001% in the same manner as in the other two groups. Urinary sodium excretion per creatinine was higher than in the other groups. The diuretic treatment inhibited body growth and suppressed adult blood pressure. While the sympathetic function was not affected, both plasma renin concentration and urinary excretion of aldosterone were elevated. These results indicate that dietary sodium restriction with the least sodium for normal growth from conception cannot blunt either the sympathetic nervous function or the development of hypertension in spontaneously hypertensive rats. Aldosterone appears to play an important role in maintaining sodium homeostasis under the dietary sodium restriction. (Hypertension. 1996;27:90-95.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We conducted this study to test the hypothesis that there are long-term effects of litter-size manipulations during the preweaning period on growth and adult blood pressure of rats. Litter size of genetically homogeneous borderline hypertensive rats, which were produced by cross-mating male Wistar-Kyoto rats with female spontaneously hypertensive rats, was manipulated from 10 to 16 days of age. In addition, a subset of males and females was castrated within the first 30 hours of life. Body weights were measured at several preweaning and postweaning ages, and tail-cuff blood pressures were recorded at 90 days of age. Intact and castrated pups of both sexes that were reared in small (n = 4) litters from 10 to 16 days of age gained nearly twice the weight of animals reared in large (n = 9 to 12) litters during this period. Intact males from small litters had significantly higher adult blood pressures than those from large litters. These long-term effects remained even in groups matched for adult weight and length. Neonatal castration of males completely blocked the consequences of litter-size manipulation on adult blood pressure, suggesting either an organizational or activational role for androgens. Neither intact nor neonatally castrated females exhibited differences in adult blood pressure as a function of litter-size manipulation. (Hypertension. 1996;27:96-101.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We designed the present study to assess any changes in plasma concentrations of the novel vasorelaxant peptide adrenomedullin in patients with essential hypertension. Plasma adrenomedullin concentrations were measured in 45 patients with untreated essential hypertension, 15 patients with borderline hypertension, and 30 normotensive control subjects. After 4 weeks of effective calcium channel blocker-based antihypertensive therapy, adrenomedullin concentrations were measured again. The concentrations were higher in hypertensive patients with increased serum creatinine levels or decreased glomerular filtration rates compared with borderline hypertensive patients and normotensive subjects, although values in normotensive and hypertensive individuals overlapped. Plasma adrenomedullin concentrations were positively correlated with serum creatinine levels and inversely correlated with glomerular filtration rates in the hypertensive patients, whereas adrenomedullin values were not correlated with blood pressure level, left ventricular mass index, or left ventricular ejection fraction. Despite blood pressure control with antihypertensive therapy, plasma adrenomedullin concentrations were not changed. Reversed-phase high-performance liquid chromatographic analysis showed that a major component of immunoreactive adrenomedullin in the plasma of normotensive subjects and hypertensive patients is human adrenomedullin-(1-52). These results indicate that plasma adrenomedullin concentrations are elevated in many hypertensive patients with renal dysfunction and its major component is human adrenomedullin-(1-52). (Hypertension. 1996;27:102-107.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

A blood pressure survey was performed in isolated Pygmy communities and Bantu population samples living either in close relationship with the Pygmies or in separate areas within the same region. The Pygmies are still living as hunter-gatherers, whereas the Bantus rely on agriculture for food provision. Mean blood pressures in Pygmies were 130/85 mm Hg in males and 126/80 mm Hg in females and in Bantus were 137/87 mm Hg in males and 136/84 mm Hg in females. In spot urine the mean urinary sodium concentration was higher in Bantus than Pygmies (86 versus 37 mmol/L in males; 95 versus 56 mmol/L in females). In the total population urinary potassium concentration was very high (150 mmol/L), calcium concentration very low (0.4 mmol/L), and urea concentration low (6.9 g/L). After adjustment for age, height, weight, and sex, no racial differences in blood pressure were present. Blood pressure increased with age but body mass index did not. Diastolic pressure correlated significantly but negatively with urinary sodium in multiple regression analysis. Our study demonstrates that blood pressure increases with age in hunter-gatherer populations on a low to moderately high sodium diet in the presence of a low urinary excretion of calcium coupled with a low protein intake. (Hypertension. 1996;27:108-113.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We previously reported that the response of the arterioles in spontaneously hypertensive rats (SHR) to histamine is blunted compared with that in normotensive control rats (Wistar-Kyoto rats [WKY]). The present study was designed to analyze the extent to which this blunted arteriolar response may be attributed in SHR to the concurrent elevation of circulating glucocorticoids through the use of adrenalectomy with and without dexamethasone supplementation. Mesenteric arterioles were observed by intravital microscopy under general anesthesia, and their lumen diameters were measured after histamine superfusion. The concentration-response curve with histamine was compared with that of an endothelium-independent vasodilator, sodium nitroprusside. At the end of each experiment, papaverine was applied topically to determine the maximal diameter for each vessel, from which a measure of arteriolar tone could be computed. The arteriolar tone in sham-operated SHR is set at a higher steady-state level than in sham-operated WKY. The concentration required for a 50% dilator response (EC50) of histamine in adrenalectomized SHR was restored to the level of WKY. Adrenalectomy did not significantly affect the EC50of histamine in WKY. When adrenalectomized SHR received a supplement of dexamethasone, the arteriolar response was found to show the same refractory pattern to histamine as sham-operated SHR. In contrast, the EC50of sodium nitroprusside in sham-operated and adrenalectomized SHR was similar to that in sham-operated WKY. Our results indicate that the impaired dilator response to histamine in SHR is related to an enhanced adrenal glucocorticoid secretion. (Hypertension. 1996;27:114-118.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Our objective was to determine whether increased salt sensitivity after menopause precedes the development of overt hypertension. We investigated the effect of ovariectomy on pressure natriuresis in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats by in vivo perfusion studies. Differences in the neural and hormonal backgrounds of the kidney were minimized by renal denervation and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. The pressure-natriuresis relationship was blunted in DS rats compared with DR rats (slope, 0.30 versus 0.63 micro mol [centered dot] min-1[centered dot] g kidney wt-1[centered dot] mm Hg-1, P < .01). The impaired pressure-natriuresis response of DS rats was further blunted by ovariectomy (from 0.30 to 0.14 micro mol [centered dot] min-1[centered dot] g kidney wt-1[centered dot] mm Hg-1, P < .05), and that of DR rats was not. The ovariectomized DS rats developed hypertension earlier than sham-operated DS rats by salt loading. These results show that ovariectomy enhances genetic salt sensitivity by blunting the pressure-natriuresis relationship, which precedes the development of overt hypertension in female DS rats. (Hypertension. 1996;27:119-124.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID