ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Identification of the quantitative trait loci that influence blood pressure and cause genetic hypertension is a major challenge. Several genetically hypertensive rat strains exist and can be used to locate by linkage analysis broad chromosomal regions containing blood pressure quantitative trait loci. Such broad chromosomal regions, and then narrower subregions, can be moved among strains (ie, production of congenic strains and congenic substrains) to identify small chromosomal regions containing the blood pressure quantitative trait loci. However, ultimate positional cloning of the quantitative trait loci presents a major difficulty because the genetic variants involved are likely to result in subtle changes in function rather than the blatant loss of function characteristic of all mendelian disease genes discovered so far by positional cloning. (Hypertension. 1995;25:1121-1128.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We have previously shown that the human adrenocortical H295R cell line expresses the type 1 angiotensin II receptor (AT1-R) and that expression of this receptor is downregulated at the level of mRNA by forskolin or dibutyryl-cAMP as well as by angiotensin II (Ang II). In this study we examine the effects of Potassium+on both AT (1) -R mRNA and receptors, as monitored through125Iodine-Ang II binding in the presence of PD 123319. After treatment with a maximal stimulatory steroidogenic dose of Potassium+(14 mmol/L), H295R cells showed an increase in cytosolic free Calcium2+from 113 to 212 nmol/L. Unlike the effects of Ang II, this increase could be abolished by pretreatment with the Calcium2+channel antagonist nifedipine (1 micro mol/L). AT1-R mRNA levels also fell in response to elevated extracellular Potassium+in a dose-dependent (Kd, 9 mmol/L; maximal fall in message at 12 mmol/L) and time-dependent (maximum 50% at 12 hours) manner. The change in AT1-R mRNA level was less rapid than that in response to activation of phosphoinositidase C by Ang II or adenylyl cyclase by forskolin or by dibutyryl-cAMP. Unlike the action of Ang II but similar to the action of forskolin or dibutyryl-cAMP, the action of Potassium+was sustained. Changes in mRNA level in response to treatment with Potassium (+), Ang II, or dibutyryl-cAMP were also paralleled by changes in125Iodine-Ang II binding in each case. The mechanism of action of Potassium+on AT1-R mRNA also appears to be mediated through the opening of voltage-sensitive channels on the plasma membrane because the drop in AT1-R mRNA was similarly abolished by the Calcium2+channel blocker nifedipine. In conclusion, our findings show that AT (1) -R mRNA levels can be controlled through a Calcium2+-dependent signaling pathway, as well as through phosphoinositidase C or adenylyl cyclase signaling pathways, and that these changes in mRNA level underlie a corresponding change in receptor protein at the cell surface. (Hypertension. 1995;25:1129-1134.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The endothelins are a family of 21-amino acid peptides that are powerful vasoconstrictors. They may also induce vascular hypertrophy. These peptides may participate through these two mechanisms in the pathogenesis of the elevation of blood pressure and/or in the maintenance of hypertension in both experimental animal models and human essential hypertension. This review presents evidence both in favor and against the involvement of endothelins in hypertension. Plasma levels of endothelin-1 are either normal or slightly elevated in experimental and human essential hypertension. Responses of blood vessels to endothelin-1 may be normal or depressed in many models of experimental hypertension and also in essential hypertension in humans. It has recently been demonstrated that endothelin content and mRNA are increased in blood vessels of deoxycorticosterone acetate-salt hypertensive rats. When endothelin receptor antagonists are administered chronically, elevation of blood pressure and development of vascular hypertrophy are blunted in this experimental model of hypertension. In contrast, spontaneously hypertensive rats do not exhibit any increase in either endothelin-1 mRNA or immunoreactive endothelin in blood vessels and fail to respond with lowering of blood pressure to long-term treatment with endothelin receptor antagonists. Blood pressure development in young spontaneously hypertensive rats is also unaffected by long-term administration of endothelin antagonists. Molecular genetic studies appear to support a genetic role of components of the endothelin system in Dahl salt-sensitive rats. In human essential hypertension, there is some evidence of activation of the endothelin system despite depressed responses of small arteries to endothelin-1 and normal circulating levels of endothelin-1 in plasma. Thus, a role of endothelins in high blood pressure is possible. Further research is necessary to establish in a more definitive way whether endothelins are involved in the pathophysiology of human essential hypertension. (Hypertension. 1995;25:1135-1143.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A sodium-reduced diet is frequently recommended for hypertensive individuals. To determine the relationship of sodium intake to subsequent cardiovascular disease, we assessed the experience of participants in a worksite-based cohort of hypertensive subjects. The 24-hour urinary excretion of sodium (USodiumV), potassium, creatinine, and plasma renin activity was measured in 2937 mildly and moderately hypertensive subjects who were unmedicated for at least 3-4 weeks. Morbidity and mortality in these systematically treated subjects were ascertained. Men and women were stratified according to sex-specific quartiles of USodiumV. Subjects in these strata were similar in race, cardiovascular status, and pretreatment and intreatment blood pressure. Subjects with lower USodiumV were thinner, excreted less potassium, and had higher plasma renin activity. During an average 3.8 years of follow-up, a total of 55 myocardial infarctions occurred. Myocardial infarction and USodiumV were inversely associated in the total population and in men but not in women, who sustained only nine events. In men, age- and race-adjusted myocardial infarction incidence in the lowest versus highest USodiumV quartile was 11.5 versus 2.5 (relative risk, 4.3, 95% confidence interval, 1.7-10.6). No association was observed between non-cardiovascular disease mortality (n = 11) and USodiumV. There was a significant linear trend in proportions of myocardial infarction by USodiumV quartile, with a break point after the lowest USodiumV quartile. In the Cox multivariate analysis, log plasma renin activity, age, systolic pressure, and cholesterol as continuous variables as well as left ventricular hypertrophy and smoking had a direct association, and USodiummV (P = .036) had an inverse, independent association with the incidence of myocardial infarction among these treated hypertensive men. (Hypertension. 1995;25:1144-1152.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Increased left atrial size has been identified as a precursor of atrial fibrillation and of stroke once atrial fibrillation is manifest. Conflicting data exist regarding the effect of high blood pressure on left atrial size. Our objective was to evaluate the association of contemporary and long-term measures of blood pressure with echocardiographically determined left atrial size in a large, population-based cohort. The study sample consisted of 1849 male and 2152 female participants of the Framingham Heart Study and Framingham Offspring Study. All analyses were sex specific. In correlation analyses, systolic and pulse pressures were identified as statistically significant determinants of left atrial size after adjustment for age and body mass index, although the magnitudes of these relations were very modest (partial r less or equal to .10). Multivariable linear regression models showed the relative contributions of the pressure variables to the prediction of left atrial size to be substantially less than those of age and, in particular, body mass index. Furthermore, inclusion of left ventricular mass in these multivariable models eliminated or attenuated the associations of the pressure variables with left atrial size. In logistic analyses, increasing levels of the pressure variables were significantly predictive of left atrial enlargement. Subjects with 8-year average systolic pressure of 140 mm Hg or higher were twice as likely to have left atrial enlargement as those with values of 110 mm Hg or lower. Overall, in this population-based study sample, increased levels of systolic and pulse pressures (but not diastolic or mean arterial pressures) were significantly associated with increased left atrial size. However, the magnitude of these associations was quite modest, particularly after controlling for age and body mass index. (Hypertension. 1995;25:1155-1160.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We studied the effects of head-down tilt to 10 degrees for 30 minutes on plasma atrial natriuretic peptide and the renin-aldosterone system in 8 preeclamptic pregnant women, 8 healthy pregnant women, and 11 nonpregnant women of fertile age. Mean arterial blood pressure did not change in the pregnant groups but increased significantly in the nonpregnant control subjects. Heart rate decreased significantly in preeclamptic women but remained unchanged in both control groups. Baseline atrial natriuretic peptide concentration was significantly higher in both preeclamptic (66 plus/minus 4 pmol/L) and pregnant (54 plus/minus 6 pmol/L) control subjects compared with non-pregnant subjects (40 plus/minus 2 pmol/L), but the difference between the pregnant groups was not significant. Head-down tilting induced a significant increase in atrial natriuretic peptide only in healthy pregnant women. Baseline plasma renin activity and aldosterone concentrations were significantly higher in pregnant control subjects compared with both the preeclamptic and nonpregnant groups. The differences between the preeclamptic and nonpregnant control groups were nonsignificant. After head-down tilting, plasma renin activity decreased significantly only in nonpregnant control subjects, whereas aldosterone decreased significantly in preeclamptic and nonpregnant control subjects. In preeclampsia, atrial natriuretic peptide release followed blood pressure and not changes in cardiac output. When all 27 women were studied, a correlation between atrial natriuretic peptide and mean arterial pressure was found in the left lateral supine position. The results suggest that pregnant women developing preeclampsia lose their usual hemodynamic control and show reactions resembling the nonpregnant state when subjected to head-down tilt. (Hypertension. 1995;25:1161-1166.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Our objective in these experiments was to evaluate the effects of atrial natriuretic factor on the gain of the spontaneous baroreceptor-heart rate reflex in humans. On two separate study days, we gave either atrial natriuretic factor during supine rest (16 nmol over 3 minutes, then 16 pmol/kg per minute) or saline (as vehicle) to nine healthy men (age, 23 plus/minus 1 years; mean plus/minus SEM) according to a random, double-blind design. Beat-by-beat RR interval and systolic pressure were recorded noninvasively. Sequences during which systolic pressure and the RR interval of the following beat changed in parallel (either increasing [Up] or decreasing [Down]) over at least three consecutive beats were identified and classified as baroreceptor-heart rate reflex sequences. Regression lines relating RR interval to the preceding systolic pressure were derived for each individual sequence. The mean value of the slopes of these regression lines was calculated to obtain the mean spontaneous baroreflex sensitivity for heart rate for each subject. Saline infusion did not change RR interval, systolic pressure, or number of baroreflex sequences nor the slope of the mean spontaneous baroreflex sensitivity for heart rate or slopes of Up or Down sequences. Atrial natriuretic factor, at a dose that lowers central venous pressure, did not affect systolic pressure, respiratory rate, or the number of baroreflex sequences but reduced RR interval from 952 plus/minus 35 to 930 plus/minus 40 ms (P < .04) and the mean slope of spontaneous baroreflex sensitivity for heart rate from 32.7 plus/minus 4.8 to 23.1 plus/minus 2.8 ms [centered dot] mm Hg-1(P < .04). Baroreflex sensitivity during Up sequences decreased during atrial natriuretic factor infusion, from 32.9 plus/minus 5.5 to 24.2 plus/minus 3.3 ms [centered dot] mm Hg-1(P < .05). The slope of Down sequences did not change (from 27.9 plus/minus 4.2 to 23.0 plus/minus 3.2 ms [centered dot] mm Hg-1) compared with baseline values, but when compared with the slope during saline infusion (35.0 plus/minus 5.2 ms [centered dot] mm Hg-1), this effect of atrial natriuretic factor on baroreflex sensitivity during Down sequences was significant (P < .05). These data indicate that atrial natriuretic factor reduces the vagal component of the arterial baroreflex control of heart rate in healthy humans. The cardioacceleration observed in humans during atrial natriuretic factor infusion may be in part due to diminished parasympathetic modulation of heart rate. (Hypertension. 1995;25:1167-1171.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The influence of intracellular renin and angiotensinogen on the control of cell-to-cell communication in heart muscle was investigated in cell pairs isolated from adult rat ventricle. Junctional conductance was measured with two separated voltage-clamp circuits. Intracellular dialysis of renin (0.2 pmol/L) caused a decrease in junctional conductance of 29 plus/minus 3.8% (plus/minus SEM, P < .05) in 7 minutes. The effect of renin on junctional conductance seems to be mainly due to the synthesis of Ang II because enalaprilat (10-9mol/L) dialyzed into the cell caused an appreciable reduction in the effect of renin. The intracellular administration of renin (0.2 pmol/L) plus angiotensinogen (0.4 pmol/L) produced a faster and stronger fall in junctional conductance (84.3 plus/minus 1.35%, P < .05), and the effect was greatly reduced by enalaprilat. The effects of both renin and angiotensinogen on junctional conductance were not related to a fall in surface cell membrane resistance or a change in series resistance. The effect of renin on junctional conductance was blocked by intracellular administration of a renin inhibitor (S 2864). Moreover, renin dialyzed into just one cell of the pair induced rectification of the junctional membrane, which was prevented by enalaprilat. The results support the view that an intracrine renin-angiotensin system in the heart regulates intercellular communication. (Hypertension. 1995;25:1172-1177.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID