摘要:

Activation of leukocytes in vivo produces marked constriction of large arteries in atherosclerotic, but not in normal, monkeys. We tested the hypotheses that vasoconstrictor responses to activated leukocytes in vivo may be abnormal during hypercholesterolemia before the development of atherosclerotic lesions and that responses may return to normal after the regression of atherosclerosis. Leukocytes were activated by injection of the chemotactic peptide formyl-methionine-leucine-phenylalanine (fMLP) into the blood-perfused hind limb of four groups of cynomolgus monkeys: monkeys fed a normal diet (normal group,n=18), monkeys fed an atherogenic diet for 3–4 months (hypercholesterolemic group,n=6), monkeys fed an athero-genic diet for 20 months (atherosclerotic group,n=19), and monkeys fed an atherogenic diet for 18 months, followed by a normal diet for 20 months (regression group,n=14). Baseline resistance of large arteries was 1.5±0.2 (mean±SEM), 2.0±0.6, 3.5±0.4 (p<0.05 versus normal), and 1.7±0.2 mm Hg/ml/min per 100 g tissue for the normal, hypercholesterolemic, atherosclerotic, and regression groups, respectively. Injection of fMLP did not change resistance of large arteries in normal or hypercholesterolemic monkeys. Injection of fMLP increased resistance of large arteries by 3.0±0.7 mm Hg/ml/min per 100 g tissue in atherosclerotic monkeys and by 1.3±0.4 mm Hg/ml/min per 100 g tissue in regression monkeys (p<0.05 versus atherosclerotic and normal). Thus, abnormal vasoconstriction in response to activation of leukocytes persists, but to a lesser extent, after regression. In contrast, vasoconstrictor responses to serotonin, which were potentiated in atherosclerotic monkeys, were normal after regression. In summary, hypercholesterolemia without arterial lesions does not result in abnormal vascular responses to activation of leukocytes. Abnormal constrictor responses of atherosclerotic arteries to activation of leukocytes are improved but not abolished after regression of atherosclerosis.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to intracerebroventricular ouabain and to mental stress and intracerebroventricular α2-adrenoceptor agonist guanabenz alone or preceded by intracerebroventricular ouabain were recorded in conscious SHR and Wistar-Kyoto (WKY) rats maintained from 4 to 8 weeks of age on different sodium diets: 1) low sodium intake (LNa, 17 μmol), 2) normal sodium intake (NNa, 101 μmol), and 3) HNa (1,370 μmol). SHR on NNa showed significantly higher MAP and RSNA compared with WKY rats on NNa. HNa or LNa significantly increased or decreased MAP but had no effects on resting RSNA in SHR and had no effects on resting MAP and RSNA in WKY rats. Intracerebroventricular ouabain induced dose-dependent increases in MAP, RSNA, and HR. In both SHR and WKY rats, LNa significantly enhanced these responses. In contrast, HNa significantly attenuated these responses only in SHR. Air stress increased and intracerebroventricular guanabenz decreased MAP, HR, and RSNA. The magnitudes of increases and decreases were significantly larger in SHR than in WKY rats. In WKY rats, dietary sodium did not change these responses. In contrast, in SHR, HNa significantly enhanced MAP, HR, and RSNA responses to air stress or intracerebroventricular guanabenz. In SHR on LNa and NNa, intracerebroventricular preinjection of ouabain enhanced the MAP, HR, and RSNA responses to air stress or intracerebroventricular guanabenz and equalized them to those in SHR on HNa. In WKY rats, preinjected ouabain did not affect responses to air stress or guanabenz. These results suggest that HNa increases brain OLA, thus decreasing responses to exogenous ouabain and that, considering its interaction with air stress and central α2-adrenoceptor stimulation, brain OLA may be involved in the central effects of dietary sodium in SHR, without exerting these effects in WKY rats, thus contributing to the differential pressor and sympathoexcitatory responses to HNa in SHR versus WKY rats.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Electrical propagation in the normal heart occurs via intercellular transfer of current at gap junctions. Alterations in intercellular coupling in the diseased heart are critical in the pathogenesis of reentrant ventricular arrhythmias. Until recently only a single gap junction protein was known to couple cardiac myocytes. We have now identified and sequenced two additional distinct gap junction proteins (connexins) expressed in the mammalian heart. The sequences differ in their predicted cytoplasmic regulatory domains. Expression of all three connexins by canine ventricular myocytes has been confirmed by Northern blotting and by immunohistochemistry with connexin-specific antisera. Immunoelectron microscopy confirmed that all three connexins are localized to myocyte gap junctions. The presence of multiple connexins in myocyte gap junctions suggests novel mechanisms for regulating cardiac electrical coupling.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID