ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Aortic smooth muscle cells from spontaneously hypertensive rats (SHR) exhibit inappropriate proliferation characteristics in culture that suggest a modified response to serum mitogens or growth factors. The present study compares vascular smooth muscle cells from SHR and normotensive Wistar‐Kyoto (WKY) rats with respect to their proliferative and functional response to growth factors. Specific attention was focused on the interaction of these vascular smooth muscle cells with epidermal growth factor. An increased growth rate of vascular smooth muscle cells from SHR (vs. WKY rats) was observed when cells were cultured in the presence of serum (10% and 0.5%), but not under serum‐free conditions. The additional presence of low serum concentrations (0.5%) was required for epidermal growth factor to elicit a proliferative response, whereupon smooth muscle cells from SHR displayed an increased (vs. WKY rats) growth rate. Saturation binding of [125I]epidermal growth factor to intact smooth muscle cells indicated a twofold increase in receptor density in SHR‐derived cells (p<0.001 vs. WKY rats) without an alteration in affinity for the growth factor. Cells derived from SHR also exhibited greater functional responsiveness to epidermal growth factor when compared with smooth muscle cells from WKY rats as evidenced by amplifications of both S6kinase activation, phosphoinositide catabolism, elevation of intracellular pH, and DNA synthesis (nuclear labeling). We conclude that increased responsiveness of SHR‐derived smooth muscle cells to epidermal growth factor could contribute to alterations in vascular smooth muscle growth and tone that may be fundamental to the pathogenesis of hypertension and atherosclerosis. (Hypertension1989;13:295‐304)

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;To investigate the role of vasoconstrictor hormones in vascular smooth muscle cell growth we have studied the effects of the potent vasoconstrictor angiotensin II on cell growth in a cultured rat aortic cell model. Angiotensin II was not mitogenic for these cells, as assessed by determining cell number, nor was it synergistic in this regard with 10% calf serum. However, 24‐hour exposure to 100 nM angiotensin II caused an 80% increase in protein synthesis (compared with 0.4% increase with serum control) as measured by tritiated leucine incorporation. This was a “hypertrophic” response as indicated by a 30% increase in protein content and a 45% increase in cell volume. Angiotensin II‐induced smooth muscle cell hypertrophy was maximal at 100 nM, had an ED50of 1 nM, and was inhibited by the competitive antagonist [Sar1, Ile8]angiotensin II. The increase in protein synthesis required continuous presence of angiotensin II for 6 hours and required messenger RNA (mRNA) synthesis as suggested by complete inhibition after exposure to actinomycin D. Angiotensin II‐stimulated protein synthesis was dependent on a rise in intracellular Ca2+concentration evidenced by a 70% decrease in tritiated leucine incorporation after chelation of Ca2+with 25 &mgr;M quin 2‐AM. This treatment did not alter protein synthesis induced by 10% calf serum. Decreasing extracellular Na+to prevent Na+/H+exchange and intracellular alkalinization did not inhibit the angiotensin II response but decreased the 10% calf serum‐stimulated protein synthesis by 35%. Downregulation of protein kinase C by 24‐hour treatment with phorbol 12,13‐dibutyrate did not inhibit angiotensin II‐induced protein synthesis, while phorbol 12‐myristate 13‐acetate‐stimulated protein synthesis was abolished. These findings suggest that angiotensin II‐induced hypertrophy, acting via a Ca2+mechanism, may play an important role in abnormal vascular smooth muscle cell growth in certain forms of hypertension. (Hypertension1989;13:305‐314)

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Blood flow pattern and morphological changes within the extracranial carotid system were studied inM. fascicularisbefore, immediately after, and at various intervals (4 hours, 4 days, 10 days, and 4 weeks) after the introduction of systemic hypertension by surgical coarctation of the thoracic aorta. Intra‐arterial hemodynamics were assessed by means of both continuous‐wave Doppler signal spectrum analysis and multigate pulsed‐wave Doppler flow velocity profile processing. Diminished peak frequencies throughout the carotid system and enlargement of the lumen diameter in the common carotid artery and the carotid bulb were major findings and were suspected to be due to cerebral autoregulation at high levels of intracranial vascular resistance. In the internal carotid artery of pure muscular type, the lumen diameter was diminished so the carotid bulb became an area of structural and hemodynamic transition. As a consequence, flow irregularities already observed in this region before surgery considerably increased during hypertension. In addition, endothelial disarray and leucocytic adherence and activation were associated with these hemodynamic alterations within the carotid bulb. Their mutual role in early atherogenesis is discussed. (Hypertension1989;13:315‐321)

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Antidiuretic hormone is known to stimulate the renal synthesis of prostaglandins. These autacoids, in turn, modulate the pressure natriuresis phenomenon. Accordingly, the present study was done to test the hypothesis that, in the absence of antidiuretic hormone and antidiuretic hormone‐dependent prostaglandin synthesis, the pressure natriuresis response is blunted. Experiments were performed on Brattleboro diabetes insipidus rats (n=7) and Long Evans control rats (n=14). A change in perfusion pressure in the Long Evans rats from 89.3±1.0 to 108.7±1.1 mm Hg (p<0.05) was associated with significant increases in the fractional excretion of sodium (1.1±0.2 to 2.3±0.3%) and the urinary prostaglandin excretion (32.6±6.8 to 56.6±10.0 pg/min). In contrast, a similar change in perfusion pressure in the diabetes insipidus rat from 88.6±1.4 to 106.2±1.5 mm Hg (p<0.05) resulted in no significant increases in either sodium or prostaglandin excretions. Treatment of a third group of diabetes insipidus rats (n=9) with 1‐desamino‐8‐D‐arginine vasopressin (1 &mgr;g/day) restored the natriuretic response to increases in renal perfusion pressure. Treated diabetes insipidus and Long Evans control rats had comparable natriuretic responses to increases in renal perfusion pressure. Untreated diabetes insipidus rats, on the other hand, had blunted responses. In summary, the pressure natriuresis response in diabetes insipidus rats is blunted compared with Long Evans control rats. We conclude that antidiuretic hormone is necessary for the complete expression of the pressure natriuresis response. (Hypertension1989;13:322‐326)

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;In the present study we examined sympathetic function and baroreceptor reflex sensitivity in adult spontaneously hypertensive rats (SHR) after a selective transection of afferent renal nerves in the prehypertensive and established phases of hypertension. Renal deafferentation performed between 3 and 4 weeks after birth did not influence the course of the development of high blood pressure when compared with sham‐operated rats. Mean arterial pressure, heart rate, and plasma norepinephrine concentrations were similar in both groups when measured at 13 weeks after renal deafferentation. However, blood pressure responses to ganglionic blockade with hexamethonium were significantly reduced in the renal deafferented SHR. Baroreceptor reflex sensitivity, assessed by heart rate responses to blood pressure changes induced by phenylephrine and nitroprusside, was significantly enhanced in these rats. When renal deafferentation was performed in adult SHR with established hypertension, mean arterial pressure decreased slightly but significantly by 5%. Heart rate, plasma norepinephrine concentrations, and responses to hexamethonium were not affected by this procedure. However, in the renal deafferented adult SHR, heart rate responses to phenylephrine but not to nitroprusside were significantly increased. Thus, in contrast to efferent renal nerves, afferent renal nerves do not play an important role in the development and maintenance of high blood pressure in SHR, but may contribute to the mechanisms that alter sympathetic function and baroreceptor reflex sensitivity in SHR during the development of hypertension. (Hypertension1989;13:327‐333)

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;We investigated the effect of atrial natriuretic factor (ANF) on aldosterone receptors in the kidney cytosol, because the binding of aldosterone to aldosterone receptors in the cytosol is considered a critical step of its action. Rat atriopeptin III was injected into male Sprague‐Dawley rats (200‐250 g) via the femoral vein while under pentobarbital anesthesia, and aldosterone receptors in the kidney cytosol were determined. The maximum binding capacity and dissociation constant were calculated by the Scatchard analysis. Maximum binding capacity of both types of aldosterone receptor (Type I, high affinity and low binding capacity and Type II, low affinity and high binding capacity) gradually decreased after ANF injection, reached the lowest level after 2 hours, and then slightly recovered. When more than 2.5 &mgr;g/kg of rat atriopeptin III was injected, the density of aldosterone receptors significantly decreased. Injection of 12.5 &mgr;g/kg of rat atriopeptin III decreased maximum binding capacity of Type I receptor from 42.3±2.4 (mean±SD,n=6) to 22.8±3.2 femtomole/mg protein (n=6)(p<0.01), and that of Type II receptor decreased from 388±46 to 285±30 fmol/mg protein (p<0.01). Dissociation constant of both types of receptors did not change significantly after ANF injection. Plasma aldosterone concentration showed no significant change after ANF injection, and a significant change was noted after ANF administration on aldosterone receptors in the experiments on adrenalectomized rats 7 days after operation. Furosemide had no significant effect on aldosterone receptors in both normal and adrenalectomized rats. These results suggest that ANF may inhibit the action of aldosterone by decreasing aldosterone receptor density in the kidney cytosol. (Hypertension1989:13:334‐340)

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;An endogenous substance in brain, clonidine‐displacing substance, binds to the same receptor populations as clonidine and is biologically active. Since receptor binding sites can be modeled by using specific antiligand antibodies, we tested the hypothesis that polyclonal antibodies raised in rat and rabbit against the clonidine analogp‐aminoclonidine coupled to hemocyanin would recognize compounds structurally related to clonidine, including clonidine‐displacing substance. Binding to anti‐p‐aminoclonidine antibodies was examined by using a competitive radioimmunoassay with tritiatedp‐aminoclonidine as the radioligand. Central vasodepressor agents that, like clonidine, are known to bind with high affinity to both imidazole sites and &agr;2‐adrenergic receptors in brain inhibited radioligand binding to anti‐p‐aminoclonidine anti‐bodies. All of these agents contain imidazol(in)e and phenyl ring moieties as part of their chemical structures (e.g., oxymetazoline); a number of other compounds without one or both of these rings failed to cross‐react with the antisera. Clonidine‐displacing substance, partially purified from bovine brain, also inhibited specific radioligand binding to anti‐p‐aminoclonidine antibodies. The inhibition was dose dependent and high affinity (IC50, 4 Units). The endogenous substance had no effect on the apparent affinity of the antibodies for the radioligand, but blocked a specific number of binding sites. Immunoprecipitation experiments showed that authentic clonidine‐displacing substance, that which displaces tritiatedp‐aminoclonidine binding to membrane receptors, is recognized by anti‐p‐aminoclonidine antibodies. We conclude that a unique subset of structural determinants required for ligand interaction with both imidazole and &agr;2‐adrenergic receptors is critical for binding to anti‐p‐aminoclonidine antibodies, and that since clonidine‐displacing substance is recognized by highly clonidine‐specific antisera, it may also contain these determinants within its structure, namely the imidazol(in)e and phenyl ring systems. (Hypertension1989;13:341‐351)

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Arterial hypertension is a common side effect of cyclosporine A therapy; however, the cellular mechanism of cyclosporine A‐induced hypertension is still unknown. The present study, therefore, examined the effect of cyclosporine A on Ca2+kinetics and contraction in primary cultures of vascular smooth muscle cells. Cyclosporine A (10 &mgr;g/ml) did not affect resting intracellular free Ca2+([Ca2+]i) levels (151±10 vs. 146±5 nM, NS), but augmented the 10−8M arginine vasopressin‐induced increase of [Ca2+]i(&Dgr;76±4 vs. &Dgr;172±6 nM,p<0.001). This effect of cyclosporine A was also observed in Ca2+‐free medium. Arginine vasopressin‐stimulated [Ca2+]iefflux within 30 seconds compared with baseline effiux rates (1,644±146 vs. 2,591±373 cpm/mg prot/30 sec,p<0.005), but this transient effect was significantly greater (p<0.001) with arginine vasopressin plus cyclosporine A (1,702±133 vs. 5,605±1235 cpm/mg prot/30 sec,p<0.01). Basal45Ca2+efflux rates were not affected by cyclosporine A, and prior incubation of the cells with cyclosporine A was required to elicit the augmentory effect.45Ca2+uptake was measured to examine the mechanism by which cyclosporine A may affect [Ca2+]istores. Cyclosporine A increased Ca2+uptake when compared with control (6.38±0.69 vs. 10.99±0.59×103cpm/mg prot/5 min,p<0.001). This effect was not blocked by the Ca2+antagonist verapamil. Arginine vasopressin (10−8M) induced contraction of smooth muscle cells with 25.5% of the cells responding. In the presence of cyclosporine A this percentage increased to 38.1±1.2%,p<0.05. These results suggest that cyclosporine A stimulates transmembrane Ca2+influx, thereby increasing arginine vasopressin‐sensitive [Ca2+]ipools in vascular smooth muscle cells. The effect of cyclosporine A to enhance vasoconstrictor‐mediated Ca2+mobilization and contraction in vascular smooth muscle cells may be an important factor in cyclosporine A‐induced hypertension. (Hypertension1989;13:352‐360)

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID