摘要:

This review summarizes some of the evidence pointing to the existence of vascular abnormalities in the spontaneously hypertensive rat (SHR) and the extent to which such abnormalities could be responsible for the elevated blood pressure in this animal. Compared with its genetic normotensive control, the Wistar-Kyoto rat (WKY), the adult SHR has an increased total peripheral resistance (TPR). Many factors appear to contribute to the increased TPR, including an active rarefication of the vascular bed and a general constriction of the vasculature. There is evidence that the general constriction is due to structural differences in the resistance vessels, to abnormally high activation levels (i.e. increased sympathetic nerve activity), and to abnormal excitation-contracting coupling within the vasculature itself (i.e. increased noradrenaline sensitivity of the vascular smooth muscle cells). Age studies and studies of the effects of antihypertensive treatment suggest that both structural and excitation-contraction abnormalities may be present before the onset of hypertension.

ISSN:1018-1172    

DOI:10.1159/000158455

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

We characterized the function of adrenergic nerve varicosities in mesenteric resistance arteries from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats by observing contractile responses to depolarization with a high potassium solution (HiK). Intact rings of resistance arteries were mounted in a specialized muscle chamber for measurement of circumferential contractile forces. Contractile responses to exogenous norepinephrine (NE), to HiK, and to the combination of NE plus HiK were significantly greater in SHR compared to WKY vessels. Using either phentolamine or 6-hydroxydopamine-treated vessels to eliminate a neurogenic adrenergic response, we determined that a part of the HiK-induced contraction was due to NE released from nerve varicosities (i.e., the adrenergic component). In order to compare these adrenergic components for possible nerve-related differences, they were first normalized to their maximum exogenous NE responses. This normalized adrenergic component of SHR vessels (52 and 58% for phentolamine and 6-hyroxydopamine treatment, respectively) was significantly greater than that of the WKY vessels (35 and 37%). This greater adrenergic component could reflect either a greater vascular smooth muscle sensitivity to NE in arteries from SHR or an increase in NE concentration, or both.

ISSN:1018-1172    

DOI:10.1159/000158456

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

Isolated rings of rabbit thoracic aorta were mounted in tissue baths for the measurement of isometric tension development and desipramine was added to all baths to block neuronal uptake of catecholamines. When these vessels were contracted to a steady-state of 1.5–3.5 g with norepinephrine, the addition of 1, 10 and 100 µM aldosterone caused a further contraction of 0.09, 0.47 and 0.8 g, respectively. Vessels contracted with norepinephrine and exposed to aldosterone were also immersed in mineral oil to trap a finite amount of norepinephrine within the receptor compartment of the tissue and the rate of relaxation was measured. The time to relax 50% (t½) in the presence of 100 µM aldosterone was approximately 18 min, while that in the presence of either ethanol diluent or 10 µM aldosterone was 7 min. When maximally effective concentrations of aldosterone and deoxycorticosterone acetate were used, the increases in norepinephrine-induced contractions and relaxation t½ values caused by these agents were identical. Combining these agents did not produce additive effects. Aldosterone also increased contractions and t½ values in tissues contracted with epinephrine but not in those contracted with methoxamine or 5-hydroxytryptamine. These findings support the conclusion that aldosterone enhances and prolongs contraction by inhibiting the removal of catecholamines from the receptor compartment of vascular smooth

ISSN:1018-1172    

DOI:10.1159/000158457

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

The purpose of this study was to investigate the effect of prior agonist-induced contraction of vascular smooth muscle on its subsequent responsiveness and maximum contractility. Repeated exposure of the rabbit ear artery to equieffective histamine (Hist) or KCl concentrations increased subsequent norepinephrine (NE) responsiveness and maximum contractility in comparison to rested controls. Tissues exposed in a similar manner to an equieffective serotonin concentration responded to NE more than did controls, but less than Hist- and KCl-pretreated tissues. Prior exposure to NE or KCl increased Hist responsiveness and maximum contractility. However, NE pretreatment did not increase serotonin or KCl responsiveness. The increased responsiveness and maximum contractility lasted for at least 90 and 390 min, respectively. When ear arteries were exposed to agonists in the presence of NaNO2 or papaverine the increase in responsiveness was either reduced or absent. Everted arteries repeatedly exposed to Hist demonstrated an increased tonic phase contraction to NE; there was no change in the initial transient phase of contraction. Exposure of the saphenous vein to Hist or KCl had no effect on subsequent NE responsiveness; however, maximum contractility was increased. The present results suggest that (1) contraction brought about by agonist drugs can result in two separate phenomena – increased responsiveness and increased maximum contractility; (2) the increased responsiveness may mask underlying α-adrenoceptor desensitization which may be agonist specific; (3) an event following agonist-receptor binding is responsible for increased responsiveness and increased maximum contractility; (4) the mechanism for increased responsiveness may be due to an increased coupling between receptor activation and membrane permeability to calcium; (5) agonist contraction in the saphenous vein and ear artery may be regulated by different mechanis

ISSN:1018-1172    

DOI:10.1159/000158458

出版商:S. Karger AG    

年代:1983

数据来源: Karger

ISSN:1018-1172    

DOI:10.1159/000158459

出版商:S. Karger AG    

年代:1983

数据来源: Karger