ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

It has long been known that the renin-angiotensin system plays an integral role in the regulation of blood pressure and electrolyte and fluid balance in mammals. The advent of molecular biologic techniques has afforded new insights into the genes regulating blood pressure. Laboratory mice and rats have been used as experimental models to examine the structural organization and expression of the renin gene. It is now well established that some mice, unlike rats and humans, contain a duplicated copy of the renin locus, which accounts for the high level of renin activity long known to be found in the submandibular gland of some mice. Indeed it is this fortuitous observation that facilitated the isolation of the first complementary DNA clones for renin and ultimately the many species-specific probes now available to analyze mammalian tissues for evidence of primary renin expression. The use of complementary DNAs as probes for primary renin expression helped confirm and further clarify earlier studies demonstrating the presence of renin activity in a number of extrarenal tissues. Although expression in some of these tissues is evolutionarily conserved, their significance has still been elusive. In this report we review the impact of molecular biology on our current understanding of renin gene structure and organization, tissue- and cell-specific expression and regulation, and the changes in renin expression throughout ontogeny. In addition, we describe how new developments in gene transfer technology have added important tools to our arsenal for examining renin gene regulation and how these technologies can be used to develop new tools for renin and hypertension research. (Hypertension 1991;18:446-457)

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Cyclosporine-induced immunosuppression has emerged as a new cause of hypertension, but the underlying mechanisms are poorly understood. In patients, this hypertension is accompanied by sympathetic neural activation. We therefore hypothesized that increased sympathetic nerve discharge is an important mechanism by which cyclosporine raises blood pressure. To test this hypothesis, we examined effects of acute administration of cyclosporine (5 mg/kg i.v.) or vehicle on renal and lumbar sympathetic nerve activity, renal and femoral blood flow velocity (pulsed Doppler flowmetry), and arterial pressure in chloralose-anesthetized rats. Vehicle had no effect on sympathetic nerve activity, whereas cyclosporine caused renal and lumbar sympathetic nerve activity to increase progressively over 60 minutes to levels that were 362 ±46% and 388 ±70%, respectively, of the baseline values (/;<0.05). These increases in sympathetic nerve activity were accompanied by proportional increases in renal and femoral vascular resistance and sustained increases in mean arterial pressure (+19±3 mm Hg,p<0.05 versus baseline). The cyclosporineinduced increases in regional vascular resistance and arterial pressure were greatly attenuated, or abolished, by ganglionic blockade or by clonidine (central sympatholysis) but were unaffected by angiotensin converting enzyme inhibition. These findings demonstrate that in an anesthetized animal preparation, the vasoconstrictor and blood pressure-raising effects of cyclosporine are caused by sympathetic neural activation.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Circulating epinephrine may facilitate neural release of norepinephrine both during and after periods of sympathoadrenal activation by stimulation of prejunctional β-adrenergic receptors. The present study was undertaken to examine possible effects and aftereffects of epinephrine on the hemodynamic reactivity to mental stress. To this end, two strictly standardized mental stress tests were performed in 14 normotensive men during and 1 hour after double-blind infusion of epinephrine (50 ngxkg-1xmin-1) or placebo given in random order. During epinephrine infusion, the systolic pressor response to psychosocial stress was augmented (+17 versus +10 mm Hg during epinephrine and placebo, respectively, p=0.02). This was associated with an attenuated post-stress recovery, with the result that the stress exposure induced a prolonged elevation of systolic blood pressure. Heart rate was elevated and diastolic blood pressure lowered during epinephrine infusion without any change in the reactivity to stress. One hour after the end of the epinephrine infusion resting heart rate was still maintained on a higher level independentiy of level of arousal, but heart rate and blood pressure responses to stress were unaffected. The findings are consistent with the hypothesis that high circulating epinephrine levels amplify pressor responses to mental stress but do not support the suggestion that short-term infusion of epinephrine causes prolonged augmentation of blood pressure responses to psychosocial stress.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The present study was performed to examine the relation between the gain of the baroreceptor reflex and the pathogenesis of hypertension in the spontaneously hypertensive rat Spontaneously hypertensive or Wistar-Kyoto rats underwent either sinoaortic baroreceptor denervation or sham denervation at 28-35 days of age. Four months later these rats were chronically instrumented for measurements of arterial pressure and heart rate. Sixty-minute computerized measurements of arterial pressure showed no difference between spontaneously hypertensive sham (163±5 mm Hg) and spontaneously hypertensive baroreceptor-denervated (166±5 mm Hg) rats, or Wistar-Kyoto sham (114±3 mm Hg) and Wistar-Kyoto baroreceptor-denervated (121 ±4 mm Hg) rats. The gain of baroreceptor reflex control of heart rate was assessed by measuring maximal heart rate responses to changes in arterial pressure elicited by bolus injection of phenylephrine and nitroprusside (gain=slope of linear regression equation of change in heart rate versus change in arterial pressure). Baroreceptor reflex gain was significantly higher in Wistar-Kyoto sham rats (‐2.10 beats/min/mm Hg) than spontaneously hypertensive sham rats (‐0.94 beats/min/mm Hg). Baroreceptor denervation significantly decreased baroreceptor reflex gain in both Wistar-Kyoto (-0.26 mm Hg) and spontaneously hypertensive (-0.22 beats/min/mm Hg) groups. Since baroreceptor denervation did not exacerbate the development of hypertension in adult spontaneously hypertensive rats or lead to hypertension in Wistar-Kyoto rats, we conclude that a primary dysfunction in the baroreceptor reflex alone is not responsible for the development of hypertension in this model.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To investigate the effects of salt loading on cardiopulmonary and arterial baroreceptor reflexes, 34 hypertensive patients underwent two 4-day periods with different dietary sodium intakes (70 and 370 meq/day). The patients were classified as salt-sensitive or salt-resistant depending on whether the mean arterial pressure value obtained on day 4 of high salt intake did or did not increase by 8% or more. In 22 patients cardiopulmonary and carotid baroreceptor reflexes were assessed during each dietary period by measuring the reflex responses to the application of‐10 mm Hg lower body negative pressure and of +60 mm Hg increase in neck tissue pressure. Salt-resistant patients (n=16) retained less sodium than salt-sensitive patients (n=6) and showed a reduction in plasma norepinephrine and forearm vascular resistance during high sodium intake, whereas the salt-sensitive patients did not During low sodium diet, no significant differences could be detected in the reflex responses to cardiopulmonary and carotid baroreceptor unloading between the two groups. High salt diet, however, potentiated the gain of cardiopulmonary baroreceptor reflex, which was expressed as the increase in plasma norepinephrine or forearm vascular resistance per millimeter of mercury decrease in pulmonary capillary wedge pressure, only in the salt-resistant hypertensive patients. In addition, the atrial natriuretic factor response to changes in pulmonary capillary wedge pressure was significantly enhanced by high salt intake only in the salt-resistant hypertensive patients. The reflex responses to carotid baroreceptor unloading were unaffected by salt loading in either group. In the remaining 12 patients, the hemodynamic effects of graded lower body negative pressure (‐5, ‐10, - 15 mm Hg) and neck tissue positive pressure (+30, +45, +60 mm Hg) were tested for both diets. Again, high salt intake significantly potentiated the cardiopulmonary baroreceptor reflex gain, expressed as the slope of the linear correlation between the changes in forearm vascular resistance (mm Hg/ml/min/100 g) and pulmonary capillary wedge pressure (mm Hg), in salt-resistant (from 3.8±0.9 to 7.2± 1.0, p<0.05) but not in salt-sensitive patients (from 4.2 ±0.9 to 3.2 ±0.6, NS). In conclusion, the present study demonstrates that high salt diet potentiates cardiopulmonary baroreceptor reflexes and enhances atrial natriuretic factor response in salt-resistant but not in salt-sensitive hypertensive patients. The salt-induced plasticity of cardiopulmonary baroreceptor reflexes may exert a protective effect against the development of salt-induced hypertension by augmenting the reflex vasodilatory response to volume expansion. Conversely, the lack of this compensatory potentiation in cardiopulmonary baroreceptor reflex function in salt-sensitive hypertensive patients might contribute to salt sensitivity.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Adenosine is an inhibitory neuromodulator in several brain regions. In the nucleus tractus soUtarius (NTS), however, adenosine exerts excitatory cardiovascular effects. The purpose of the present study was to elucidate the involvement of other endogenous mechanisms that could contribute to the final hemodynamic response to adenosine in this nucleus. In normotensive Sprague-Dawley rats, intra-NTS microinjection of adenosine (23 nmol/60 nl) decreased blood pressure and heart rate. These effects were blocked by prior administration of the specific adenosine receptor antagonist l,3-dipropyl-8-p-sulfophenylxanthine (0.92 nmol) and by the two glutamate receptor antagonists kynurenic acid and glutamic diethylester. The specificity of the adenosine-glutamate interaction in the NTS was demonstrated with adrenergic and angiotensin receptor antagonists that did not affect the adenosine response and by experiments with glutamate receptor antagonists that did not affect nicotine actions in the NTS. Furthermore, an increase in glutamate levels was demonstrated during perfusion of adenosine through a microdiatysis probe in the NTS of anesthetized rabbits. These findings indicate that adenosine increases the release of glutamate in the NTS and, thus, are at variance with the concept of a "universal" inhibitory effect of adenosine in the central nervous system.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The paraventricular hypothalamus regulates autonomic nerve outflow and is innervated with β-endorphin-immunoreactlve nerve terminals. This study examined the effects of β-endorphin microinjected into the paraventricular hypothalamus on blood pressure, heart rate, and plasma catecholamine and glucose concentrations in conscious, unrestrained spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at the age of about 9 weeks. Thirty minutes after paraventricular hypothalamic injection of [125I]β-endorphin (3.5 fig), most of the recovered radioactivity was detectable within ±0.5 mm from the injection site in the coronal, sagittal, and horizontal planes. Unilateral paraventricular hypothalamic injections of 0-endorphin (I and 0.1 μg/0.1 μl) increased blood pressure and heart rate in both strains in a dose-independent manner with significantly greater increases in SHR. Plasma catecholamine and glucose concentrations were measured 15, 30, and 60 minutes after /J-endorphin injection. Norepinephrine concentrations were not significantly altered in WKY rats but increased in SHR. Epinephrine concentrations increased in both strains with significantly greater increases in SHR. Increases in catecholamine concentrations were not dose-related. Glucose concentrations also increased in both strains with significantly greater increases in SHR only at the lower dose. Ganglionic blockade with pentolinium significantly reduced 0-endorphin-induced pressor and tachycardiac responses in SHR. Pretreatment of the paraventricular hypothalamus with naltrexone (1.1 μg) in SHR blocked the initial pressor and tachycardiac responses to 0-endorphin (0.1 μg) and blunted increases in epinephrine and glucose levels. When the animals were anesthetized with o-chloralose 2-5 days after the study in conscious animals, there were no differences in blood pressure or heart rate between strains after β-endorphin (0.1 fig) injection. The results indicate that conscious SHR show enhanced cardiovascular and sympathoadrenal responses to β-endorphin injected into the paraventricular hypothalamus, suggesting that alterations in the activity of the paraventricular hypothalamic β-endorphin system can modulate the development of hypertension in SHR. (Hypertension 1991;18:503-515)

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Abundant experimental data suggest that an endogenous digitalislike factor is responsible for some essential hypertension. Some forms of hypertension have also been associated with increased levels of catecholamines. We therefore designed experiments to investigate the role of digitalislike factors in the regulation of norepinephrine turnover in the neurovascular junction. We chose bufalin, an amphibian-derived compound that shares many of the physiological properties postulated as characteristic of digitalislike compounds, as a model of the mammalian compound. In vitro experiments in canine saphenous veins showed that, in addition to inhibiting norepinephrine uptake, bufalin increased norepinephrine overflow by an amount larger than could be explained solely by uptake inhibition. The effect of bufalin on norepinephrine overflow is inhibited by tetrodotoxin, which suggests a dependence of this response on Na+ influx through the neuronal membranes. We propose that Na+,K+-ATPase inhibition resulting in neuronal depolarization is responsible for the augmented norepinephrine turnover caused by bufalin and that these indirect effects of norepinephrine on the cardiovascular system may play a role in the etiology of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Chronic treatment of rats with the naturally occurring androgen, testosterone, leads to hypertension and cardiovascular disease. This effect is believed to be mediated through the adrenal gland and in particular by action on the steroid 11±-hydroxylase enzyme system. To study the possible mechanism of this effect, the enzyme system was examined at several time periods up to the time that hypertension develops. Rats were treated with testosterone (10 mg/day) for 3, 7, 21, and 42 days. Levels of cytochrome P-45011βenzyme and messenger RNA (mRNA) were determined as well as 11β-hydroxylase enzyme activity. A significant decrease in enzyme activity was observed after 3 days of treatment This correlates with a profound decrease in the level of cytochrome P-45011βenzyme as determined by Western blot analysis. A large decrease in cytochrome P-45011βmRNA was also observed after 3 days of treatment All three parameters remained low throughout the treatment period. The decrease in 11β-hydroxylase enzyme activity appears to result from a lower enzyme level brought about by decreased concentrations of mRNA transcripts.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID