摘要:

The cardiac hypertrophy observed in hypertension is thought to be responsible for the accompanying deficiency in the baroreflex control of heart rate. In this study, we assessed the baroreflex relationship between heart rate and arterial pressure in a group of seven rabbits during a normotensive period, during the early phase of angiotensin II (Ang II)-induced hypertension (1 week) (50 ng/kg per minute IV via osmotic minipumps), after 7 weeks of continuous hypertension, then 2 days after Ang II was stopped, and finally 7 days after Ang II. Left ventricles were weighed for measurement of left ventricular weight-body weight ratio. One week of intravenous Ang II infusion produced hypertension (mean arterial pressure from 80 +/- 2 up to 115 +/- 8 mm Hg), with significantly increased heart rate and hematocrit. The heart rate-arterial pressure baroreflex curve was shifted to the right, with a significant 45% reduction in the gain of the reflex (-6.4 +/- 1.5 to -3.5 +/- 0.2 beats per minute/mm Hg). After 7 weeks of Ang II, arterial pressure was still elevated (112 +/- 4 mm Hg) and the gain of the baroreflex curve still somewhat attenuated, although it was no longer markedly different from normotensive levels (gain, -5.09 +/- 0.95, 20% reduction from normotensive level). Two days after the Ang II infusion was stopped, arterial pressure had returned to normotensive levels, although hematocrit and heart rate remained elevated. At this time, the baroreflex curve was similar to prehypertensive control levels, with no further changes when measured again 7 days after Ang II. Cardiac hypertrophy was present when measured at 7 days after angiotensin (left ventricular weight-body weight ratio: 1.78 +/- 0.05 versus 1.35 +/- 0.04 g/kg, hypertensive versus normotensive, P < .05). Thus, although Ang II infusion produced an initial deficit in the baroreflex control of heart rate, this effect became less as the hypertension continued. Furthermore, although cardiac hypertrophy developed, its presence did not appear to be sufficient to produce a decrease in barosensitivity independent of raised arterial pressure. (Hypertension. 1997;29:1284-1290.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We recorded changes in arterial blood pressure, heart rate, and renal sympathetic nerve activity in response to intracerebroventricular injection of bovine hypothalamic/hypophysary inhibitory factor and ouabain in conscious Wistar rats. Ouabain at 0.3 to 0.6 micro gram caused dose-related increases in blood pressure, heart rate, and nerve activity (peak increases: 19 +/- 2 mm Hg, 42 +/- 4 beats per minute, and 48 +/- 4%, respectively; P < .05 versus basal). These responses were all blocked by central antibody Fab fragments, which bind ouabain and related steroids with high affinity. The inhibitory factor significantly increased blood pressure but decreased heart rate and nerve activity. Dose-dependent increases in blood pressure as well as heart rate and nerve activity were observed when the inhibitory factor was injected after intravenous injection of the vasopressin antagonist D-(CH2)5Tyr-(Me)AVP. Central Fab fragments, however, did not affect these responses. Both ouabain and the inhibitory factor inhibited Na+, K (+) -ATPase activity in vitro. Fab fragments blocked this inhibition by ouabain but not by the inhibitory factor. These data indicate that the ouabainlike sympathoexcitatory effect of this factor is masked probably by a potent central effect on vasopressin release. In contrast to rat brain "ouabain," this factor does not exhibit a high affinity for the Fab fragments, supporting the previous finding that this compound is structurally a nonouabain Na+, K+-ATPase inhibitor. (Hypertension. 1997;29:1291-1295.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Shear stress is known to dilate blood vessels and exert antiproliferative effects on vascular walls; these effects have been ascribed to shear stress-induced upregulation of endothelium-derived vasoactive substances, mainly nitric oxide and prostacyclin. We have demonstrated the significance of C-type natriuretic peptide (CNP) as a novel endothelium-derived relaxing peptide (EDRP) that shares a cGMP pathway with nitric oxide. Adrenomedullin is a recently isolated EDRP that elevates intracellular cAMP as prostacyclin does. To elucidate the possible role of these EDRPs under shear stress, we examined the effect of physiological shear stress on CNP mRNA expression in endothelial cells derived from the human umbilical vein (HUVECs), bovine aorta (BAECs), and murine lymph nodes (MLECs) as well as adrenomedullin mRNA expression in HUVECs. CNP mRNA was stimulated prominently in HUVECs under shear stress of 15 dyne/cm2in a time-dependent manner (4 hours, sixfold increase compared with that in the static condition; 24 hours, 30-fold increase). Similar results were obtained in BAECs (4 hours, twofold increase; 24 hours, threefold increase) and MLECs (4 hours, threefold increase; 24 hours, 10-fold increase). Augmentation of CNP mRNA expression that was dependent on shear stress intensity was also observed (5 dyne/cm2, 2.5-fold increase of static; 15 dyne/cm2, 4.5-fold increase). Increased CNP secretion was also confirmed by the specific radioimmunoassay for CNP. Adrenomedullin mRNA expression in HUVECs increased under shear stress of 15 dyne/cm2in a time-dependent manner (4 hours, 1.2-fold increase of static; 24 hours, threefold increase) and shear stress intensity-dependent manner (15 dyne/cm2, threefold increase compared with that at 5 dyne/cm2). These results suggest that the coordinated augmentation of mRNA expression of these novel EDRPs may constitute shear stress-dependent vasodilator and antiproliferative effects. (Hypertension. 1997;29:1296-1302.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

To assess whether patients with mild essential hypertension have excessive activities of the sympathoneuronal and adrenomedullary systems, we examined total body and forearm spillovers and norepinephrine and epinephrine clearances in 47 subjects with mild essential hypertension (25 men, 22 women, aged 38.1 +/- 6.7 years) and 43 normotensive subjects (19 men, 24 women, aged 36.5 +/- 5.9 years). The isotope dilution method with infusions of tritiated norepinephrine and epinephrine was used at rest and during sympathetic stimulation by lower body negative pressure at -15 and -40 mm Hg. Hypertensive subjects had a higher arterial plasma epinephrine concentration (0.20 +/- 0.01 nmol [center dot] L-1; mean +/- SE) than normotensive subjects (0.15 +/- 0.01) (P < .01). The increased arterial plasma epinephrine levels appeared to be due to a higher total body epinephrine spillover rate in the hypertensive subjects (0.23 +/- 0.02 nmol [center dot] min-1[center dot] m-2) than the normotensive subjects (0.18 +/- 0.01) (P < .05) and not to a decreased plasma clearance of epinephrine. The arterial plasma norepinephrine level, total body and forearm norepinephrine spillover rates, and plasma norepinephrine clearance were not altered in the hypertensive subjects. The responses of the catecholamine kinetic variables to lower body negative pressure were not consistently different between normotensive and hypertensive individuals. These data indicate that individuals with mild essential hypertension (1) have elevated arterial plasma epinephrine concentrations that are due to an increased total body epinephrine spillover rate, indicating an increased adrenomedullary secretion of epinephrine; (2) have no increased generalized sympathoneuronal activity and no increased forearm norepinephrine spillover; and (3) have similar responses of both the sympathoneuronal and adrenomedullary systems to sympathetic stimulation by lower body negative pressure. (Hypertension. 1997;29:1303-1308.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The migration of coronary artery medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in coronary atherosclerotic lesions. In the current study, we examined the possible interaction of adrenomedullin, a novel vasorelaxant peptide, and angiotensin II (Ang II) on human coronary artery SMC migration using Boyden's chamber method. Ang II stimulated SMC migration in a concentration-dependent manner between 10-6and 10-8mol/L. This stimulation was clearly blocked by the Ang II type 1 receptor antagonist losartan but not by the type 2 receptor antagonist PD 123319. The migration stimulatory effect of Ang II was chemotactic in nature for cultured human coronary artery SMCs but was not chemokinetic. Human adrenomedullin clearly inhibited Ang II-induced migration in a concentration-dependent manner. Human adrenomedullin stimulated cAMP formation in these cells. Inhibition by adrenomedullin of Ang II-induced SMC migration was paralleled by an increase in the cellular level of cAMP. 8-Bromo-cAMP, a cAMP analogue, and forskolin, an activator of adenylate cyclase, inhibited the Ang II-induced SMC migration. These results suggest that Ang II stimulates SMC migration via type 1 receptors in human coronary artery and adrenomedullin inhibits Ang II-induced migration at least partly through a cAMP-dependent mechanism. Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, this peptide may play a role as a local antimigration factor in certain pathological conditions. (Hypertension. 1997;29:1309-1313.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Cyclosporine causes various platelet abnormalities. Whether it affects the ability of platelets to mediate vasodilation is unknown. Platelets were isolated from healthy volunteers and 13 heart transplant patients on cyclosporine. When perfused through preconstricted normal rabbit carotid arteries, activated platelets from transplant patients failed to cause vasorelaxation, whereas normal platelets produced significant vasodilation (-4.0 +/- 1.9% versus 30 +/- 3% [P < .0001] change in vessel diameter, respectively). When normal platelets were exposed to cyclosporine in vitro, they lost their ability to cause vasodilation in a dose- and time-dependent fashion. However, when activated and perfused through quiescent, Nomega-nitro-L-arginine-pretreated arteries, platelets from transplant patients and normal platelets caused similar degrees of vasoconstriction. The amount of adenosine triphosphate in the supernatant from activated cyclosporine-exposed and control platelets was similar (1.7 +/- 0.4 versus 1.5 +/- 0.3 micro mol/L [P = NS], respectively). However, concomitant perfusion of activated platelets from transplant patients impaired acetylcholine-mediated, endothelium-dependent vasodilation but perfusion of normal platelets did not. Although cyclosporine-exposed platelets showed an impaired ability to produce vasorelaxation, supernatant from the same platelets caused near normal vasodilation. Human platelets exposed to cyclosporine have an impaired ability to mediate vasodilation. This is not due to increased platelet-mediated vasoconstriction or a decrease in the release of platelet-derived nucleotides but rather to a short-acting compound released by cyclosporine-exposed platelets that interferes with endothelium-dependent vasodilation. (Hypertension. 1997;29:1314-1321.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The aim of the present work was to further characterize intracellular calcium stores released by angiotensin II (Ang II) in spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) vascular smooth muscle cells (VSMCs) and to study their alterations associated with proliferation. Intracellular Ca2+concentration was monitored by image analysis in aortic myocytes loaded with fura 2. In the presence of extracellular Ca2+, sensitivity to Ang II in proliferating VSMCs was not different in the two strains, but it increased 10-fold in confluent VSMCs from SHR compared with those from WKY. In Ca2+-free medium, Ca (2+) release induced by thapsigargin (10 micro mol/L) was significantly greater (about twofold) in SHR than WKY, in both proliferating and confluent cultures, with responses during proliferation being 0.7-fold smaller. Responses to Ang II were abolished after exposure of the cells to thapsigargin. In proliferating cultures, ryanodine (10 micro mol/L) did not modify the rises in intracellular Ca2+concentration induced by Ang II in VSMCs from both strains. Conversely, in confluent cultures, ryanodine reduced Ang II (100 nmol/L)-induced Ca2+release to the same level as in proliferating cultures, and it suppressed the difference between SHR and WKY. These results show that the ryanodine-sensitive Ca (2+) release induced by Ang II is enhanced in VSMCs from SHR at confluence and is impaired during proliferation. Thus, they suggest that differences in Ca2+-induced Ca2+release from the sarcoplasmic reticulum may participate in increased responsiveness of VSMCs to Ang II in SHR and in phenotypic modulation of vascular myocytes during proliferation. (Hypertension. 1997;29:1322-1328.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The purpose of this study was to test the hypothesis that differences in voltage-gated Ca2+channels increase with age during the development of sustained hypertension in the spontaneously hypertensive rat (SHR). Using patch-clamp methods, we measured whole-cell Ca2+currents in freshly isolated myocytes from small mesenteric arteries of juvenile (5 to 7 weeks), young (10 to 12 weeks), and mature (19 to 23 weeks) Wistar-Kyoto rats (WKY) and SHR. Indirect tail artery systolic pressure increased progressively with age in SHR (from 125 +/- 5 to 159 +/- 5 to 192 +/- 5 mm Hg) but only in the younger WKY (from 107 +/- 6 to 130 +/- 4 to 136 +/- 4 mm Hg). Peak Ca2+current density (current per cell capacitance) was larger in SHR than WKY myocytes at all ages (at 6 weeks, 3.5 +/- 0.4 versus 2.3 +/- 0.2 pA/pF; at 12 weeks, 3.8 +/- 0.2 versus 3.1 +/- 0.2; at 20 weeks, 4.9 +/- 0.4 versus 3.3 +/- 0.4). Cell capacitance (surface area) was significantly smaller in 12-week-old SHR than WKY (25.2 +/- 1.1 versus 31.8 +/- 1.6 pF), but no differences were found in the 6- or 20-week-old groups. There were significant differences in Ca2+current with strain, age, and voltage but no significant age-strain interactions. The ratio of peak Ca2+current for SHR to that of WKY declined linearly with voltage at all ages, suggesting differences in the voltage dependence of Ca2+current activation. The voltage dependence of Ca2+current was shifted to the left in SHR compared with WKY at all ages. Activation curves were shifted significantly in the negative voltage direction only in 20-week-old SHR myocytes. We have found differences with age in Ca2+current density and its voltage dependence in SHR compared with WKY during the phase of development in which blood pressure becomes established in the SHR. The net effect of these differences predicts a larger Ca2+current in SHR at voltages in the physiological range of membrane potential. (Hypertension. 1997;29:1329-1336.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We have isolated from bovine hypothalamic and pituitary tissues a sodium pump inhibitor that is structurally different from ouabain. By mass spectrometric analysis, this purified factor revealed a single unique molecular ion with an accurate mass of 412.277 and a mass spectra different from that of ouabain. It has been previously shown that this factor inhibits the Ca2+, Mg2+-ATPase of the plasma membrane of synaptosomes. Because Ca2+plays a major role in cellular excitability, we carried out a systematic study of the effects of this inhibitor on the Ca2+transport processes across the plasma membrane of synaptosomes: We measured ATP-dependent calcium uptake, Na+-Ca (2+) exchange, and passive permeability using45Ca2+and Millipore filtration, chlortetracycline fluorescence, and light-scattering, respectively. This factor inhibits the Na+, K+-ATPase activity of the synaptosomal plasma membrane vesicles in the same range of concentrations that produced an increase of intrasynaptosomal free calcium, with nearly the same K0.5 value. In addition, in this concentration range, this factor stimulated 10- to 11-fold the passive flux of Ca2+and 2.5- to 3-fold the Ca2+influx via the Na+-Ca2+exchange in these membranes with respect to control values. Measurements of fluorescence anisotropy showed that in this concentration range, the inhibitor did not significantly change the order parameter (fluidity) of these membranes. These results suggest that besides its known inhibition of the sodium pump, this factor could play a role in the control of Ca2+homeostasis by direct modulation of transport systems implicated in the control of intracellular calcium. (Hypertension. 1997;29:1337-1343.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

In rat atria isolated with their cardioaccelerans nerves and labeled with [(3) H]norepinephrine, exposure to 1 x 10-7mol/L angiotensin II (Ang II) and 1 x 10-7mol/L Ang-(1-7) increased the release of radioactivity elicited by nerve stimulation (0.5-millisecond-long square-wave pulses at 2 Hz during 2 minutes) by 90% and 60%, respectively. The facilitatory effect on noradrenergic neurotransmission caused by both peptides was stereospecifically prevented by Nomega-nitro-L-arginine methyl ester (1 x 10-4mol/L), an inhibitor of nitric oxide synthase that catalyzes the conversion of L-arginine to nitric oxide, as well as by 1 x 10-5mol/L methylene blue, a substance that inhibits the guanylate cyclase considered as the final target of nitric oxide action. On the other hand, the precursor of nitric oxide synthesis, L-arginine (1 x 10-3mol/L), reversed the prevention produced by Nomega-nitro-L-arginine methyl ester on the increased release of norepinephrine caused by Ang II and Ang-(1-7). The present results suggest that nitric oxide could be involved in the neuromodulatory function elicited by both Ang II and Ang-(1-7) in rat atria. The physiological role of this observation is still under study. (Hypertension. 1997;29:1344-1350.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID