摘要:

Isolated hand arteries and veins from healthy human subjects were tested in vitro for their contractile response to adrenergic agonists and 5-hydroxytryptamine (5-HT) under standardized conditions. This allowed for quantitative estimation of various receptor characteristics. The relative sympathomimetic potency suggested α-adrenergic receptors, which was confirmed in Schild plots following phentolamine antagonism of the response (pA2 for artery 7.57, for vein 7.75). 5-HT contracted with a relative potency approximately equal to noradrenaline and adrenaline in arteries, but only one fifth to one tenth of the catecholamine activity in veins. Ketanserin inhibited the 5-HT response in a competitive, probably also irreversible, manner in arteries (pA2 9.50, KA 8.90 × 10–7 M). In the veins, ketanserin counteracted the 5-HT-induced contraction in a noncompetitive

ISSN:1018-1172    

DOI:10.1159/000158579

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The ability of angiotensin to enhance the field-stimulation induced release of 3H-norepinephrine from the superfused rat portal vein was examined in vessels obtained from animals fed a normal (0.5% Na+) or low sodium diet (0.05% Na+). Angiotensin was seen to enhance the field-stimulation (480 pulses, 2 Hz, 1 ms duration, supramaximal voltage) induced release of 3H-norepinephrine from vessels obtained from Sprague-Dawley, Wistar, Wistar-Kyoto (WKY) and the spontaneously hypertensive rats (SHR) maintained on a normal sodium diet. The effect of angiotensin was attenuated when examined in vessels obtained from animals maintained on the low sodium diet. The selectivity of the low sodium diet for angiotensin was demonstrated by a lack of effect of the low sodium diet in altering the facilitatory effect of isoproterenol on the release of 3H-norepinephrine and an enhanced response to the α2-adrenoceptor-selective antagonist, yohimbine. The simultaneous treatment of rats with a low sodium diet plus captopril (estimated to be approximately 50 mg/kg/day for 7 days) prevented the attenuation of the angiotensin-induced enhancement of the release of 3H-norepinephrine seen by sodium alone. These results are consistent with the hypothesis that low sodium treatment increases circulating angiotensin levels which lead to a down-regulation of the angiotensin receptors located on adrenergic nerve varicosities

ISSN:1018-1172    

DOI:10.1159/000158580

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

In order to evaluate vascular (myogenic) and tubular (tubuloglomerular feedback) mechanisms involved in renal blood flow (RBF) autoregulation, canine kidneys with filtration (normal) and without filtration (nonfiltering, NFK; ureteral-obstructed, UO) were studied. RBF was monitored in response to stepwise reductions in renal perfusion pressure of –20, –40, and –60 mm Hg from control pressure. None of the three groups demonstrated significant changes in RBF from their respective control values (normal, 380 ml/min/100 g; NFK, 179 ml/min/100 g; UO, 153 ml/min/100 g) until the lowest pressure (–60 mm Hg from control pressure). All three groups responded to the pressure reductions with significant decreases in renal vascular resistance. However, the calculated efficiency of the autoregulatory response for the NFK and UO groups was significantly less than for the normal group. Elimination of tubuloglomerular feedback (NFK and UO) did not necessarily eliminate renal vascular autoregulation, but did reduce the efficiency of autoregulation. It is suggested that both vascular (myogenic) and tubular (tubuloglomerular) mechanisms may coexist to efficiently autoregulate blood flow in normal filtering kidneys. However, a reduction in metabolic activity as a contributor to the reduced ability to autoregulate in these kidneys could be an additional poss

ISSN:1018-1172    

DOI:10.1159/000158581

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The accumulation of (–)-3H-adrenaline (3H-A) by rabbit isolated aorta was studied. In all experiments, monoamine oxidase and catechol-O-methyltransferase were inhibited by treatment with pargyline and 3’,4’-dihydroxy-2-methyl-propiophenone (U-0521), respectively. The relationship between the accumulation of 3H derived from 3H-A (10–8 M) and the duration of incubation (0–3 h) was linear. The 3H-accumulation after 3 h incubation was 22.5 ml·g-1. In reserpine-treated tissue, the 3H-accumulation levelled off after 30 min and was 8.5 ml·g–1 after 3 h. The concentration of 3H-A or (–)-3H-noradrenaline (3H-NA) and the 3H-accumulation (ml·g–1) were inversely related. At 10–8 M, the 1-hour accumulation of 3H derived from 3H-A and 3H-NA was 7.8 and 15.2 ml·g–1, respectively. With increasing concentrations (3 × 10–8–10–4 M), the accumulation values approached each other. At 10–4 M, the accumulation was 2.3 and 2.8 ml·g-1 for 3H-A and 3H-NA, respectively. The accumulation of 3H derived from 3H-A (10–8–10–4 M) by reserpine-treated tissue also showed an inverse relationship with concentration: 5.4 ml·g-1 (10–8 M) and 2.6 ml·g–1 (10–4 Af). The accumulation of 3H derived from 3H-A (10–8 M; 1 h) was dependent on the bath temperature (1–37 °C). The accumulation increased continuously from 1.1 ml·g–1 (1 °C) to 11.1 ml·g-1 (37 °C). Storage of tissue (0–5 days in salt solution without equilibration with 95% O2/5% CO2; 4 °C) did not affect the accumulation of 3H derived from 3H-A (10–8 M; 1 h). Thereafter (7–14 days), the accumulation decreased. The inhibitory potency (IC5o; –log M) of desimipramine, cocaine, (–)-propranolol, (–)-isoprenaline, and (±)-normetanephrine on accumulation of 3H derived from 3H-A (10-8 M; 1 h) was found to be 8.26; 6.50; 5.48, 4.88, and 4.02, respectively. The maximal degree of inhibition was almost the same for these drugs, while that of clonidine and corticosterone was 50 and 20%, respectively. In the presence of desimipra-mine (10–6 M), either clonidine (10–5–10–3 M), corticosterone (10–6–10–4 M) or (-)-isoprena-line (10–5–10–3 M) reduced the accumulation of 3H derived from 3H-A (10–8 M; 1 h). Oua-bain (3 × 10–4 M) and iodoacetic acid (10–3 M), but not sodium cyanide (10–3 M) and 2,4-dinitrophenol (10–3 M), reduced the accumulation of 3H derived from 3H-A (10–8 M; 1 h). Anoxia (95% N2/5% CO2; 37 °C; 1–24 h) did not alter the accumulation of 3H derived from 3H-A (10–8 M; 1 h). D-(+)-Glucose deprivation alone or combined with anoxia markedly reduced the 3H-accumulation. These results suggest that adre

ISSN:1018-1172    

DOI:10.1159/000158582

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Cyclic 3’,5’-adenosine monophosphate (cAMP) accumulation and morphological changes induced by isoproterenol (ISO) on cultured vascular smooth muscle cells (SMC) and vascular fibroblasts derived from spontaneously hypertensive rats, their stroke-prone strain and normotensive Wistar Kyoto rats were investigated. At the time points studied, ISO-induced cAMP accumulation in SMC reached a peak level at 5 min. Accumulation was dose-dependent and was maximal at a concentration of 10–5 M ISO. Maximal cAMP levels were approximately 600-fold higher than basal levels. Maximal cAMP accumulation or half maximal stimulatory ISO concentrations were similar in SMC from the three strains. ISO had no effects on cyclic 3’,5’-guanosine monophosphate (cGMP) levels in SMC. Phenylephrine had no effects on cAMP or on cGMP levels. In contrast to SMC, β-adrenergic stimulation of vascular fibroblasts resulted in only a 4-fold increase of cAMP levels. 1.5 h after administration of ISO to SMC cultures, the morphological changes were apparent in SMC but not in fibroblasts. Morphological changes induced by ISO were reversible and morphological appearances returned to normal 16 h after exposure to ISO. 10-3 M dibutyryl cAMP had similar effects on the moφhologies of both SMC and fibroblasts. These effects were antagonized by 5 × 10–6 M colchicine, an inhibitor of microtubule assembly. These results indicate that cultured vascular SMC possess the ability to increase markedly their cellular cAMP level in response to β-adrenergic stimulation, while fibroblasts are less responsive to the stimulation. Furthermore, cAMP accumulation results in morphological changes of SMC and fibroblasts probably through the alteration of intracellular microtubule systems. As the morphological response to intracellular cAMP (or its lipophilic derivatives) is similar in both SMC and fibroblasts, the difference in each cell line’s responsiveness to ISO may be due to a difference in: (1) the density or sensitivity of β -adrenergic receptors on the plasma membrane of each cell type, or (2) the catalytic activity of adenyl

ISSN:1018-1172    

DOI:10.1159/000158583

出版商:S. Karger AG    

年代:1985

数据来源: Karger