摘要:

This study examined the role of endogenous kinins in the alteration of renal hemodynamics induced by low-dose converting enzyme inhibition in hydropenic normotensive rats and in the nonclipped kidney of hydropenic two-kidney, one clip hypertensive rats. Infusion of a bradykinin B2receptor antagonist (D-Arg0,[Hyp3,Thi5,8, D-Phe7]-bradykinin, 1 or 10 micro gram [centered dot] kg-1symbol* min-1) did not alter renal function of normotensive rats. In a second series of experiments, infusion of enalaprilat at 0.1 mg [centered dot] kg-1[centered dot] h-1increased renal blood flow (P < .01) and decreased renal vascular resistance (P < .01). The superimposition of the kinin antagonist at 1 micro gram [centered dot] kg-1[centered dot] min-1during the enalaprilat infusion decreased renal blood flow to a value similar to the preenalaprilat baseline and significantly different from the mean of the two enalaprilat periods before and after the addition of the kinin antagonist--the "mean effect of enalaprilat." The decrease in renal blood flow induced by the kinin antagonist was associated with an increase in renal vascular resistance above the mean effect of enalaprilat (P < .025). In two-kidney, one clip hypertensive rats, systemic infusion of enalaprilat augmented the hemodynamics of the nonclipped kidney by a degree similar to that in normotensive rats. In contrast to normotensive rats, superimposition of the kinin antagonist did not alter the enalaprilat-induced change in blood flow or vascular resistance of the nonclipped kidney. The results of this study suggest that endogenous kinins contribute to the increased renal function induced by low-dose converting enzyme inhibition in hydropenic normotensive rats but appear to contribute less to the enalaprilat-induced alterations of renal function in the nonclipped kidney of two-kidney, one clip hypertensive rats. (Hypertension. 1996;27:235-244.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The objective of this study was to determine whether the calcium antagonist amlodipine could slow the progression of chronic renal disease. We examined the effects of amlodipine on kidney structure and function in two experimental models of hypertension. In the first study, adult, male Munich Wistar rats underwent uninephrectomy and were given weekly injections of desoxycorticosterone and 1% saline for drinking. Rats ingested normal chow or chow containing amlodipine for 8 weeks. The drug reduced systemic blood pressure, but glomerular filtration rate, kidney weight, proteinuria, and morphological evidence of glomerular injury were not affected. In the second study, male spontaneously hypertensive rats underwent uninephrectomy at 5 weeks of age and were followed for 6 months, during which they received no therapy or amlodipine. The drug dose was determined in preliminary studies to be the highest dose not associated with marked growth retardation. Again, although systemic blood pressure was significantly reduced by amlodipine, proteinuria and the prevalence of glomerulosclerosis were similar in amlodipine-treated and control spontaneously hypertensive rats. Micropuncture studies revealed that glomerular pressure remained elevated in amlodipine-treated spontaneously hypertensive rats. Kidney weight and glomerular volume were also similar in amlodipine-treated and control rats. Amlodipine also failed to inhibit platelet aggregation. Therefore, antihypertensive therapy with amlodipine fails to reduce glomerular pressure in spontaneously hypertensive rats as well as glomerular size and injury in spontaneously hypertension rats and desoxycorticosterone-salt hypertension. Although other dihydropyridine calcium antagonists have been found to reduce experimental glomerular injury, these data suggest that amlodipine may not prevent hypertensive nephrosclerosis. (Hypertension. 1996;27:245-250.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

110 g/m2125 g/m2in men). Voltage of the QRS complex was integrated over the total QRS duration in leads X and Z for calculation of the time-voltage integral of the horizontal plane vector complex. With the use of a partition of 99.2 micro Vanadium [centered dot] s with a specificity of 98% in the entire normal group, sensitivity of the horizontal plane vector integral was significantly lower in women than men (31% versus 71%, P < .001). In contrast, use of sex-specific partitions of 75.4 micro Vanadium [centered dot] s in women and 99.2 micro Vanadium [centered dot] s in men with matched 98% specificity significantly improved sensitivity in women to 81% (P < .001), with no change in sensitivity in men (71%). Comparison of receiver operating characteristic curves with the use of sex-specific criteria demonstrated no significant difference in overall performance of the horizontal plane vector integral between men and women. The 81% and 71% sensitivities of the sex-specific horizontal plane vector integral were significantly greater than the 27% to 58% sensitivities of sex-specific 12-lead electrocardiographic criteria in this population. Thus, sex-specific criteria significantly improve performance of the time-voltage integral of the QRS for the identification of left ventricular hypertrophy in women, with no loss of accuracy in men. Use of the time-voltage integral can improve the accuracy of the electrocardiogram for the identification of left ventricular hypertrophy in both women and men. (Hypertension. 1996;27:251-258.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Endothelin-1, a potent vasoconstrictor produced by vascular endothelial cells, activates the hypertrophic program in cultured heart muscle cells. However, the role of endothelin-1 in cardiac hypertrophy in humans is unknown. Therefore, we studied hypertrophic cardiomyopathy patients with normal pulmonary arterial pressure, in whom cardiac hypertrophy is a specific feature of the disease. Radioimmunoassay with a monoclonal antibody to human endothelin-1 showed that the plasma level of immunoreactive endothelin was more than twofold higher in hypertrophic cardiomyopathy patients than in control subjects (P < .005). In situ hybridization analysis of endomyocardial biopsy specimens showed positive signals of endothelin-1 type A receptor mRNA in ventricular myocytes of all specimens. The receptor expression in ventricular myocytes was similar between hypertrophic cardiomyopathy patients and control subjects. We propose that endothelin-1 might represent an important factor involved in hypertrophic cardiomyopathy. Whether endothelin-1 plays a causal role in cardiac hypertrophy or is a marker of its occurrence needs to be clarified. (Hypertension. 1996;27:259-264.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We investigated the influence of beta-adrenergic receptor activation on the control of gap junctional conductance (gj) in the heart of cardiomyopathic hamsters (11 months old). We measured gj in isolated ventricular cell pairs using two voltage-clamp circuits. Administration of isoproterenol (10-6mol/L) to the bath had no effect on gj in myopathic cell pairs but increased gj by 45 plus/minus 3% (plus/minus SE) in normal hamsters. Moreover, forskolin (10-7mol/L), an activator of adenyl cyclase, did not change gj in myopathic cells but enhanced gj by 23 plus/minus 2.8% in controls. Similar results were obtained with isobutylmethylxanthine (10-6mol/L), a phosphodiesterase inhibitor. Dibutyryl-cAMP (10-6mol/L), however, increased gj of cardiomyopathic cell pairs by 58 plus/minus 2.1% within 2 minutes and enhanced gj in controls by 50 plus/minus 3.6%. The effect of dibutyryl-cAMP on gj of myopathic cells was suppressed by intracellular dialysis of an inhibitor of protein kinase A. These observations indicate that the regulation of gj by the beta-adrenergic receptor-G protein-adenyl cyclase signaling system is greatly impaired in the failing heart but the ability of cAMP to increase gj is still preserved. (Hypertension. 1996;27:265-268.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Angiotensin II (Ang II) and arginine vasopressin (AVP) increased intracellular free Calcium2+concentration [Calcium2+] (i) and/or the [Calcium2+]itransient rate (CaTR) in cultured neonatal rat cardiomyocytes. These agents increased membrane-bound protein kinase C (PKC) with peak activity at 5 and 10 minutes, respectively. Two-minute exposure to Ang II produced homologous desensitization to a repeated stimulation with Ang II and heterologous desensitization to AVP. Two-minute exposure to AVP also produced homologous desensitization to AVP but not heterologous desensitization to Ang II. When the AVP exposure time was increased from 2 to 10 minutes coincident with maximal AVP-mediated PKC activation, heterologous desensitization to Ang II was also observed. Acute activation (15 minutes) of PKC by phorbol 12-myristate 13-acetate (PMA) blocked responsiveness to both Ang II and AVP. When PKC activation was inhibited by 20 hours of prior exposure to PMA, as confirmed by PKC assay, homologous desensitization of Ang II still occurred, confirming an alternative mechanism(s) for homologous desensitization in the cardiomyocytes. In contrast, 20-hour PMA suppression of PKC markedly diminished the ability of the cardiomyocytes to exhibit AVP-mediated heterologous desensitization for Ang II. These data indicate that PKC activation plays a primary role in mediating vasopressin Vanadium1receptor-induced heterologous desensitization of the Ang II receptor and participates in a hierarchy of two or more kinase systems mediating homologous desensitization of the Ang II receptor in cardiomyocytes. (Hypertension. 1996;27:269-275.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The relationship between resting levels of muscle sympathetic nerve activity (MSA) and blood pressure is a matter of controversy. Body weight has recently been identified as an independent determinant of muscle sympathetic discharge, which may have influenced previous studies focused on MSA and mechanisms of hypertension. In the present study, we measured resting MSA and plasma insulin levels in 18 obese (body mass index, 32 plus/minus 4 kg/m2) (mean plus/minus SD), middle-aged (52 plus/minus 6 years), hypertensive (155 plus/minus 11/97 plus/minus 8 mm Hg) subjects and 16 age- and body mass index-matched normotensive control subjects. In the postabsorptive state, resting MSA was similar in the hypertensive and normotensive groups (43 plus/minus 4 versus 39 plus/minus 3 bursts per minute, 69 plus/minus 5 versus 64 plus/minus 5 bursts per 100 heart beats, P = NS) (mean plus/minus SEM) and did not correlate with either systolic or diastolic blood pressure. Weak but significant positive correlations were found between resting MSA and both fasting insulin levels (P < .05) and body mass index (P = .05) in hypertensive but not normotensive subjects. There was a strong positive correlation between fasting insulin and body mass index in both normotensive subjects and the entire study group (P < .005). Fasting insulin and body mass index correlated with diastolic blood pressure (P < .05) in the entire study group. In conclusion, a relationship between fasting insulin, body mass index, and blood pressure was confirmed, whereas only a weak correlation was found between MSA and fasting insulin in hypertensive but not normotensive subjects. The fact that MSA was similar in the two groups argues strongly against augmented MSA being important for the maintenance of hypertension, at least in middle-aged, obese men. (Hypertension. 1996;27:276-280.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The present study was designed to determine the developmental changes in intrarenal angiotensin (Ang) peptides in the rat. Kidney Ang I and II levels were threefold and sixfold higher in newborn than adult kidneys, respectively (Ang I, 678 plus/minus 180 versus 243 plus/minus 38 fmol/g, P < .01; Ang II, 667 plus/minus 75 versus 103 plus/minus 6 fmol/g, P < .001). Intrarenal Ang II levels correlated positively with the temporal changes in renin gene expression (r = .93, P < .001). However, no correlation was found between renal Ang II content and angiotensin-converting enzyme (ACE) expression during development, which prompted us to evaluate whether renal enzymes, other than renin and ACE, contribute to Ang II formation in the developing kidney. Angiotensin peptide levels were measured in newborn and adult kidney homogenates incubated with human angiotensinogen (a poor rat renin substrate) for 30 minutes at 37 degrees Celsius. Inhibitors of aspartyl proteases and metalloproteases were ineffective in preventing the formation of Ang II in either newborn or adult kidneys. However, addition of the serine protease inhibitors soybean trypsin inhibitor and phenylmethylsulfonyl fluoride inhibited Ang II generation in the newborn kidneys only. In contrast, Ang I generation was not affected by inhibition of serine proteases in either newborn or adult kidneys. We conclude that Ang I and II synthesis is activated in the developing rat kidney. In addition to renin and ACE, the newborn rat kidney expresses serine protease activity that is capable of generating Ang II directly from angiotensinogen. This putative enzyme is induced in the newborn kidney and may cooperate with renin in the activation of Ang II synthesis during early development. (Hypertension. 1996;27:281-286.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Previous studies have shown that angiotensin II (Ang II) can activate cardiovascular neurons within the medulla oblongata via an action on specific receptors. The purpose of this study was to determine the distribution of neurons within the medulla activated by infusion of Ang II into the fourth ventricle of conscious rabbits, using the expression of Fos, the protein product of the immediate early gene c-fos as a marker of neuronal activation. Experiments were done in both intact and barodenervated animals. In comparison with a control group infused with Ringer's solution alone, in both intact and barodenervated animals, fourth ventricular infusion of Ang II (4 to 8 pmol/min) induced a significant increase in the number of Fos-positive neurons in the nucleus of the solitary tract and in the rostral, intermediate, and caudal parts of the ventrolateral medulla.

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We and other laboratories have reported that arterial baroreflex-mediated control of heart rate is blunted in spontaneously hypertensive rats (SHR) compared with normotensive controls. Recently, we reported that atrial natriuretic peptide (ANP) microinjected into the caudal nucleus tractus solitarii of SHR further blunts this defect. The present study tested the hypothesis that ANP modulates arterial baroreflex-mediated control of sympathetic nervous system activity. Nine-week-old, male SHR (n = 29) and normotensive Wistar-Kyoto control rats (n = 24) were instrumented for microinjection into the caudal nucleus tractus solitarii and for direct measurement of arterial blood pressure, heart rate, and lumbar sympathetic nervous system activity. After urethane- and alpha-chloralose-induced anesthesia, arterial baroreflex-mediated control of heart rate and lumbar sympathetic nerve activity was assessed during phenylephrine- (5 to 40 micro gram [centered dot] kg-1[centered dot] min-1) induced increases and sodium nitroprusside- (15 to 300 micro gram [centered dot] kg-1[centered dot] min-1) induced decreases in mean blood pressure before and after microinjection of ANP (50 ng) or monoclonal antibody to ANP (0.55 micro gram) into the caudal nucleus tractus solitarii. ANP reduced and the antibody enhanced the sensitivity of baroreflex-mediated control of both heart rate and lumbar sympathetic nerve activity in SHR but not in Wistar-Kyoto controls (P < .05). Arterial baroreflex sensitivity was unchanged with control microinjections of vehicle or mouse IgG in SHR. These data suggest that endogenous ANP in the caudal nucleus tractus solitarii may contribute to the development and/or maintenance of hypertension in SHR by blunting baroreflex-mediated control of sympathetic nervous system activity. (Hypertension. 1996;27:297-302.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID