摘要:

Resistance to the capacity of insulin to suppress lipolysis may be an important link in the association between abdominal obesity and hypertension. Furthermore, a more active renin-angiotensin system in adipose tissue may contribute to insulin-resistant lipolysis in abdominally obese hypertensive subjects. We determined nonesterified fatty acid concentrations and turnover as well as lipid oxidation under basal conditions and during steady-state euglycemia with two levels of insulinemia (72 and 287 pmol/L) in lean normotensive, abdominally obese normotensive, and abdominally obese hypertensive subjects. To assess the role of the renin-angiotensin system in determining non-esterified fatty acid turnover, we repeated studies in the abdominally obese hypertensive subjects after double-blind random assignment to placebo or enalapril for 1 month each. The main findings were the following: (1) Nonesterified fatty acid flux was significantly higher in abdominally obese hypertensive subjects at both levels of insulinemia than in either abdominally obese normotensive or lean normotensive subjects and correlated significantly with both mean blood pressure and total systemic resistance during the higher level of insulinemia. (2) Enalapril significantly improved insulin-resistant lipolysis in the abdominally obese hypertensive subjects. The improvement in insulin suppressibility of nonesterified fatty acid flux at the high hormonal concentrations correlated positively with the magnitude of reduction in blood pressure. (3) Basal lipid oxidation and suppression in response to insulin were similarly impaired in both obese groups. Resistance to the antilipolytic actions of insulin is thus a characteristic feature in abdominally obese hypertensive subjects and may be linked to the elevated blood pressure in these individuals. A more active renin-angiotensin system may partly explain the insulin-resistant lipolysis in this form of hypertension. (Hypertension. 1996;28:120-126.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The development of insulin resistance may be an early step in the development of hypertension; however, the mechanism for this process is not known. The worsening of insulin resistance and hypertension could increase both systemic and glomerular capillary pressures and predispose an individual to renal injury. The purpose of this study was to examine the relationship of insulin resistance to glomerular hemodynamics and dietary salt intake in 10 older (68 plus/minus 6 years), obese (body mass index, 31 plus/minus 4 kg/m2), mildly hypertensive (151 plus/minus 8/82 plus/minus 2 mm Hg), sedentary subjects without clinical evidence of diabetes or renal disease. They were studied on separate days with radioisotopic renal clearances (glomerular filtration rate by99mTc-diethylenetriaminepentaacetic acid urinary clearance; renal plasma flow by131Iodine-hippuran serum disappearance) and a two-dose (40 and 100 mU/m2per minute) hyperinsulinemic euglycemic clamp for measurement of glucose disposal after 2 weeks of a 3-g and 2 weeks of a 10-g sodium diet. Glomerular filtration rate (68.1 plus/minus 7.7 to 78.0 plus/minus 6.6 mL/min per 1.73 m2, P = .08) and glomerular filtration fraction (0.21 plus/minus 0.02 to 0.22 plus/minus 0.02, P = .5) did not change significantly after dietary salt was increased. During low dietary salt intake, there was an inverse relationship between glomerular filtration fraction and glucose disposal rate (milligrams per kilogram fat-free mass per minute) at both low (r = -.70, P = .04) and high (r = -.83, P = .006) insulin levels. However, these relationships were attenuated during salt loading. This suggests that a greater degree of insulin resistance, not increased dietary salt, may predispose older mildly hypertensive subjects to renal injury by worsening renal hemodynamics through the elevation of glomerular filtration fraction and resultant glomerular hyperfiltration. (Hypertension. 1996;28:127-132.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Although research in population studies has indicated that recent alcohol intake is positively correlated with blood pressure, there is a need to study the relationship of blood pressure to measures of lifetime alcohol intake in alcoholics. To this end, we assessed systolic and diastolic pressures and lifetime alcohol intake through structured interviews with 253 normotensive recovering alcoholics. Blood pressures were first corrected with multiple linear regression for the influence of confounding or modifying variables and then were regressed against alcohol consumption measures. Systolic pressure was significantly correlated (positively) with only a few measures of recent alcohol intake, and the correlations were not high (r2= .05 to .11, P < .05). Diastolic pressure was found to be highly and positively correlated with the duration of the drinking career, but more so in blacks than in whites. The total lifetime dose of alcohol was found to be positively correlated with diastolic but not systolic pressure, but only in black male alcoholics. The steeper slope of the regression of blood pressure versus lifetime total alcohol or duration of the drinking career in black alcoholics suggests greater cardiovascular susceptibility to alcohol toxicity as lifetime doses increase and as the drinking career lengthens. (Hypertension. 1996;28:133-138.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We investigated the relationship between sodium sensitivity and diurnal variation of blood pressure in patients with essential hypertension. Twenty-eight inpatients with essential hypertension were maintained on high sodium (12 to 15 g NaCl per day) and low sodium (1 to 3 g NaCl per day) diets for 1 week each. Twenty-four-hour blood pressure and urinary sodium excretion were measured at the end of each diet period, and the sodium sensitivity index was calculated as the ratio of the change in mean arterial pressure to the change in urinary sodium excretion rate by sodium restriction. Patients whose average mean arterial pressure was lowered more than 10% by sodium restriction were assigned to the sodium-sensitive group (n = 16); the remaining patients, whose mean arterial pressure was lowered by less than 10%, were assigned to the non-sodium-sensitive group (n = 12). In the non-sodium-sensitive group, mean arterial pressure and heart rate fell during the nighttime, and average values of systolic, diastolic, and mean arterial pressures during the night were significantly lower than those during the day during both low and high sodium diets. On the other hand, in the sodium-sensitive group, there was no nocturnal fall in mean arterial pressure, and none of the systolic, diastolic, and mean arterial pressure values during the nighttime was different from the respective pressure values during the daytime during either sodium diet. The sodium sensitivity index was positively correlated with the fall in mean arterial pressure during the nighttime during a high sodium diet (r = .55, P < .01). These results indicate that in patients with sodium-sensitive essential hypertension, blood pressure fails to fall during the night. High sodium sensitivity may be a marker of greater risk of renal and cardiovascular complications, as has been found in nondippers, patients whose blood pressure fails to fall during the night. (Hypertension. 1996;28:139-142.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We examined whether the effect of Y-26763, an ATP-sensitive potassium channel opener, on cerebral blood flow is altered in stroke-prone spontaneously hypertensive rats (SHRSP) and, if altered, whether long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor, is capable of preventing the change. Cerebral blood flow during intracarotid infusion of Y-26763 was measured in anesthetized SHRSP and normotensive Wistar-Kyoto rats (WKY) as control. Y-26763 increased cerebral blood flow in a dose-dependent manner in WKY, and glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, inhibited the Y-26763-induced increase in cerebral blood flow. In contrast, the response to Y-26763 in SHRSP was significantly impaired compared with that in WKY. Antihypertensive treatment with cilazapril lowered blood pressure toward normal and prevented the impaired response in cerebral blood flow to Y-26763 in SHRSP. These findings suggest that (1) ATP-sensitive potassium channels contribute to the regulation of cerebral blood flow in rats, (2) the response to an ATP-sensitive potassium channel opener is markedly diminished in hypertensive rats, and (3) the altered response to an ATP-sensitive potassium channel opener during chronic hypertension can be prevented by long-term antihypertensive treatment. (Hypertension. 1996;28:143-146.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We administered liposome-encapsulated antisense oligodeoxynucleotide targeted to angiotensinogen mRNA peripherally to spontaneously hypertensive rats to test whether peripheral angiotensinogen reduction would lower their hypertensive blood pressures and to determine the role of peripheral angiotensinogen in the modulation of hypertension. Using in vitro translation techniques, we tested the sequence specificity of the antisense sequence. The selected antisense sequence decreased angiotensinogen production in vitro, enabling us to distinguish between specific and nonspecific effects. To increase the efficiency of peripheral and hepatic antisense delivery, oligonucleotides were liposome encapsulated for intra-arterial administration. Confocal microscopy was used for determination of the hepatic distribution of fluorescently labeled antisense. Encapsulated antisense molecules were seen to be distributed within liver tissue 1 hour after injection; however, little or no uptake was observed with the unencapsulated oligonucleotides. We also determined the physiological effects of antisense oligodeoxynucleotide targeted to liver angiotensinogen mRNA. Administration of liposome-encapsulated antisense significantly decreased hypertensive blood pressures to normotensive levels compared with scrambled control oligonucleotides, unencapsulated antisense, and empty liposomes (P = .013). These data were supported by biochemical changes elicited by the antisense treatment. Rats receiving liposome-encapsulated antisense had significantly lowered peripheral angiotensinogen and angiotensin II levels compared with control groups (P < .05). No significant heart rate changes were observed in the antisense or control groups. These results suggest that peripheral angiotensinogen plays a role in the maintenance of hypertensive blood pressure in this model of hypertension and that peripheral administration of antisense molecules is possible with organ-targeted delivery mechanisms. (Hypertension. 1996;28:147-151.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID