摘要:

Aldosterone, the most important mineralocorticoid, regulates electrolyte excretion and intravascular volume mainly through its effects on renal distal convoluted tubules and cortical collecting ducts. Excess secretion of aldosterone or other mineralocorticoids or abnormal sensitivity to mineralocorticoids may result in hypertension, suppressed plasma renin activity, and hypokalemia. Such conditions often have a genetic basis, and studies of these conditions have provided valuable insights into the normal and abnormal physiology of mineralocorticoid action. Deficiencies of steroid 11 beta-hydroxylase or 17 alpha-hydroxylase are types of congenital adrenal hyperplasia, the autosomal recessive inability to synthesize cortisol. These two defects often cause hypertension because of overproduction of cortisol precursors that are, or are metabolized to, mineralocorticoid agonists. These disorders result from mutations in the CYP11B1 and CYP17 genes encoding the corresponding enzymes. Glucocorticoid-suppressible hyperaldosteronism is an autosomal dominant form of hypertension in which aldosterone secretion is abnormally regulated by corticotropin. It is caused by recombinations between linked genes encoding closely related isozymes, 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), generating a dysregulated chimeric gene with aldosterone synthase activity. Apparent mineralocorticoid excess is a loss of functional ligand specificity of the mineralocorticoid receptor caused by a deficiency of the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase, an enzyme that normally metabolizes cortisol to cortisone to prevent cortisol from occupying the receptor. This autosomal recessive form of severe hypertension results from mutations in the HSD11K (HSD11B2) gene. (Hypertension. 1996;28:927-936.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In normal subjects, the level and variability of blood pressure decrease during non-rapid eye movement (non-REM) sleep. In contrast, sleep apnea is associated with large swings in nocturnal pressure. In this study, we evaluated a computer-derived index of all-night blood pressure variability in normotensive snorers with or without sleep apnea. We also examined this index in snorers receiving medical treatment for coexistent ischemic heart disease. Beat-to-beat blood pressure was recorded with a photoplethysmographic device (Finapres) throughout polysomnography. Subjects were categorized into four groups: those without cardiovascular disease without or with sleep apnea (greater or equal to 15 apnea plus hypopnea per hour of sleep), and those with ischemic heart disease without or with sleep apnea. A frequency distribution histogram of all increases and decreases of blood pressure according to their amplitudes was drawn and the SD of the distribution used as an estimation of variability. Mean systolic and diastolic pressures during the total sleep time were not different among the four groups. In contrast, the SD of the distribution of systolic and diastolic pressure variations that were higher in the apneic than in the nonapneic groups (P < .05) correlated with apnea plus hypopnea (P <.0001) and transient electroencephalographic arousal number per hour of sleep (P < .0001). In both apneic and nonapneic subjects, blood pressure variability as assessed by SD decreased during stages 3 and 4 of non-REM sleep compared with stages 1 and 2 and REM sleep (P < .001). Blood pressure variability was similarly increased in apneic subjects with or without ischemic heart disease. We speculate that in apneic individuals with coexistent ischemic heart disease, pressure variability that is increased despite treatment with beta-blockers or calcium antagonists may be a risk factor for acute coronary events. (Hypertension. 1996;28:937-943.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity. (Hypertension. 1996;28:944-952.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Uncertainty still remains regarding the differing effects of blood pressure and age on baroreceptor-cardiac reflex sensitivity in elderly individuals; these differences are at least partly due to the differing methods and subject groups used in previous studies. We sought to resolve these issues by examining baroreflex sensitivity in 54 subjects aged 70 +/- 1 years (mean +/- SE; range, 60 to 81) divided into groups with combined systolic-diastolic hypertension (CH group, n = 16), isolated systolic hypertension (ISH group, n = 16), or normotension (NT group, n = 22). Baroreflex sensitivity was quantified from the pulse interval and blood pressure responses to the Valsalva maneuver and pressor (phenylephrine) and depressor (sodium nitroprusside) stimuli. Baroreflex sensitivity was significantly reduced in the two hypertensive groups but did not differ between them (Valsalva maneuver: CH group, 1.9 +/- 0.3 ms/mm Hg; ISH group, 2.8 +/- 0.5; NT group, 4.4 +/- 0.4; phenylephrine: CH group, 3.1 +/- 0.6; ISH group, 3.5 +/- 0.7; NT group, 7.7 +/- 1.0; sodium nitroprusside: CH group, 2.1 +/- 0.3; ISH group, 3.6 +/- 0.8; NT group, 5.4 +/- 0.3; all P < .05 for comparison with the NT group). Thus, this study demonstrated reductions in baroreflex sensitivity with hypertension in elderly subjects consistent across all methods but with no difference between subjects with combined hypertension and isolated systolic hypertension matched for similar systolic pressure. Baroreflex sensitivity was related only to the level of systolic pressure independent of diastolic pressure or age. If elderly subjects with isolated systolic hypertension have a greater reduction in large-artery compliance than combined hypertensive subjects with similar systolic pressure, this does not appear to lead to further reductions in baroreflex sensitivity in these individuals. (Hypertension. 1996;28:953-960.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In vitro and animal studies have demonstrated that the effect of angiotensin II (Ang II) on aldosterone is mediated through the Ang II type I receptor. However, it has been difficult to demonstrate an effect of Ang II type I receptor blockade on aldosterone levels in human studies. One possible explanation is that subjects have not been studied under salt-controlled conditions. Therefore, we examined the effects of losartan on the aldosterone and renal plasma flow responses to Ang II infusion in six normotensive subjects under low and high salt conditions. Ang II was infused in graded doses (0.3 to 10 ng/kg per minute) in the presence and absence of losartan (a single 50-mg oral dose). Renal plasma flow was assessed by measurement of para-aminohippurate clearance. Blood pressure, plasma aldosterone levels (low salt conditions only), and para-aminohippurate clearance were measured before and after each Ang II dose. Losartan had no effect on baseline systolic pressure but attenuated the systolic pressure response to exogenous Ang II during both low salt (0.7 +/- 1.9 versus 6.7 +/- 1.4 mm Hg, P = .001) and high salt (2.0 +/- 1.9 versus 12.3 +/- 2.1 mm Hg, P = .006) conditions. Under low salt conditions, losartan reduced the baseline plasma aldosterone level from 1135 +/- 204 to 558 +/- 102 pmol/L (P = .015) and blocked the aldosterone response to Ang II (-49 +/- 110 versus +436 +/- 83 pmol/L, P = .019). During high salt conditions, losartan had no effect on baseline renal plasma flow but attenuated the renal plasma flow response to Ang II (-90.1 +/- 15.1 versus -185.1 +/- 2.6 mL/min per 1.73 m2, P = .013). These data confirm that losartan lowers both basal and exogenous Ang II-stimulated aldosterone levels under low salt conditions. Losartan does not significantly affect baseline renal plasma flow but does attenuate the renal plasma flow response to exogenous Ang II under high salt conditions. (Hypertension. 1996;28:961-966.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Nitric oxide seems to be involved in the mechanisms underlying the antihypertensive and renal responses of losartan in spontaneously hypertensive rats (SHR). We investigated the contribution of nitric oxide to the effect of this angiotensin II (Ang II) type 1 (AT (1)) receptor antagonist on the constrictor response of phenylephrine in aortic rings from SHR. Furthermore, since it has been suggested that Ang II could bind to unblocked AT2receptors, during administration of an AT1receptor antagonist, we also studied the effect of the AT (2) receptor antagonist PD 123319 on the contractile response to phenylephrine in aortic rings from SHR. To this end, we studied dose-response curves of phenylephrine (10-9to 10-5mol/L) in the presence and absence of losartan (10-9, 10-7, and 10-5mol/L) in SHR aortic rings. Preincubation with losartan reduced the constrictor response to phenylephrine but not to KCl (10 to 120 mmol/L) in a dose-dependent manner. On the other hand, the presence of captopril (10-5mol/L) in the incubation medium did not alter the response to phenylephrine, even at the dose of 10-3mol/L. The reduced response to phenylephrine in the presence of losartan was abolished in both endothelium-denuded rings and rings treated with a nitric oxide synthesis inhibitor. A similar situation was observed in PD 123319-pretreated rings, in which the effect of losartan on the contractile response to phenylephrine was reversed. Losartan was not able to stimulate the production of aortic cGMP compared with the control group. Likewise, losartan did not modify the relaxing responses to either acetylcholine or sodium nitroprusside in phenylephrine-preconstricted aortic rings. Furthermore, losartan did not alter isometric tension in aortic rings in either basal or phenylephrine-preconstricted conditions. These data demonstrate that Ang II potentiates the vasoconstriction induced by phenylephrine through the stimulation of AT1receptors. Moreover, AT2receptors and nitric oxide appear to be involved in this effect. (Hypertension. 1996;28:967-972.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

T helper cells and macrophages infiltrate into the renal cortical interstitium during the course of hypertensive nephrosclerosis. To investigate the mechanisms of mononuclear cell infiltration, we examined the expression of the intercellular adhesion molecule-1 (ICAM-1) and its counterpart lymphocyte function-associated antigen-1 (LFA-1) in the progression of hypertensive renal injury. We studied nonclipped kidneys of two-kidney, one clip renovascular hypertensive and sham-operated control rats immunohistochemically at 4, 7, 14, and 28 days after clipping (n = 5 per group and time point). Systolic pressure was significantly elevated by day 7 (154 +/- 4 versus 117 +/- 6 mm Hg in sham, P < .05). The development of hypertension resulted in a progressive increase of ICAM-1 expression in the perivascular and interstitial areas of the renal cortex and on proximal tubular brush borders. Only a few glomeruli showed augmented ICAM-1 staining. Increased ICAM-1 was associated with an accumulation of LFA-1-positive mononuclear cells in the perivascular region (day 14: 15 +/- 4 versus 2 +/- 0.2 cells/mm2in sham, P < .005) and intertubular region (127 +/- 11 versus 32 +/- 3 cells per millimeter squared in sham, P < .005). The maximum was obtained at day 14 and remained elevated until day 28. In addition, the number of interstitial LFA-1-positive infiltrating cells was related to the degree of interstitial and tubular ICAM-1 expression and correlated with blood pressure (r = .75, P < .001, n = 18). Our data suggest that ICAM-1 is involved in the recruitment of macrophages/lymphocytes via specific interaction of ICAM-1 and LFA-1 in this model of hypertensive target-organ damage. (Hypertension. 1996;28:973-979.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We used antisense obligodeoxynucleotide (ODN) strategy, based on interference of information flow from gene to protein, to determine the role of kininogen and bradykinin B2receptor genes in the pathogenesis of genetic hypertension in rats. Mean blood pressure of 9-week-old spontaneously hypertensive rats (SHR) increased 4 hours after acute intracerebroventricular injection of synthetic 18-mer antisense ODNs targeting the translation initiation codon of kininogen mRNA (from 164 +/- 5 to 181 +/- 4 mm Hg, P < .01) or bradykinin B2receptor mRNA (from 161 +/- 5 to 185 +/- 8 mm Hg, P < .01) and then returned to basal levels within 24 hours. Prolonged vasopressor effects were observed after repeated injections of antisense ODN targeting kininogen mRNA. Antisense ODNs to kininogen and B2receptor mRNAs increased blood pressure of normotensive Wistar-Kyoto rats only slightly compared with SHR (from 116 +/- 3 to 124 +/- 1 and from 116 +/- 2 to 126 +/- 4 mm Hg, respectively; P < .05). Cardiovascular responses were confirmed by the use of antisense ODNs targeted to bind to different non-overlapping regions of kininogen or B2receptor mRNA. Microinjection of antisense ODN to B2receptor mRNA into the nucleus tractus solitarii increased mean blood pressure in SHR and prevented the vasodepressor effect induced by intranuclear microinjection of bradykinin. No significant change in mean blood pressure was induced in either strain by intravenous injection of antisense ODNs or by central injection of sense or scrambled ODNs. A strong fluorescent signal was detected at the level of the hippocampus, thalamus, hypothalamus periventricularis, midbrain, and cerebrum 1 hour after central injection of fluorescein isothiocyanate-conjugated antisense ODNs. Kininogen levels were significantly lower in the brain of rats given intracerebroventricular antisense kininogen ODN compared with controls. Our results indicate that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure and suggest that this system may exert a protective action against further elevations of blood pressure levels in SHR. (Hypertension. 1996;28:980-987.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

120 g/m2) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean + 3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m (2). The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-terminal ANP or N-terminal ANP-(1-30) has potential utility for the detection of altered left ventricular structure and function in a patient population at risk for cardiovascular disease. (Hypertension. 1996;28:988-994.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

To examine the pathophysiological mechanisms in transgenic rats carrying the murine Ren-2drenin gene, we studied atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression and secretion in 12-week-old hypertensive TGR(mREN-2)27 and normotensive Sprague-Dawley rats. Hypertension and marked left ventricular hypertrophy in TGR(mREN-2)27 rats were associated with high baseline plasma levels of immunoreactive ANP (148 +/- 18 versus 34 +/- 3 pmol/L, hypertensive versus normotensive rats; P < .001), whereas plasma immunoreactive BNP levels did not differ significantly between the strains (19 +/- 4 versus 12 +/- 3 pmol/L, P = .06). ANP mRNA and immunoreactive ANP levels in the left ventricular endocardial and epicardial layers in TGR(mREN-2)27 rats were about 20 to 40 times higher (P < .001) than those in normotensive rats. There were no statistically significant differences between atrial and ventricular BNP mRNA levels, but left ventricular immunoreactive BNP concentrations were twofold higher in hypertensive TGR(mREN-2)27 than in normotensive rats. Infusion of [Arg8]-vasopressin (0.05 micro gram/kg per minute IV, for 2 hours) in normotensive rats produced rapid increases (twofold, P < .05 to .01) in left ventricular BNP mRNA and immunoreactive BNP levels, whereas ventricular BNP mRNA and peptide levels did not change significantly in hypertensive rats. The increase in left atrial BNP mRNA levels in response to acute pressure overload was also significantly smaller in the hypertensive than normotensive rats (3.5-fold versus 5.2-fold, P < .01). Furthermore, the proportional but not absolute (in picomoles per liter) increase in plasma immunoreactive ANP was smaller in transgenic rats in response to acute saline and [Arg8]-vasopressin infusions (0.9% NaCl: 1.9-fold increase versus 4.4-fold increase in normotensive rats, P < .001; [Arg8]-vasopressin: 2.2-fold versus 4.8-fold increase, P < .001). These results show that baseline and cardiac overload-induced increases in BNP synthesis are markedly attenuated in transgenic rats carrying the murine Ren-2drenin gene. In addition, acute volume and pressure overload produced a smaller proportional increase in ANP secretion in hypertensive rats than normotensive rats. These alterations in the natriuretic peptide system may contribute to the pathogenesis of hypertension and cardiovascular complications in the TGR(mREN-2)27 rat. (Hypertension. 1996;28:995-1004.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID