ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:It has been postulated that hypertension in the spontaneously hypertensive rat (SHR) results from autoimmune damage to the SHR vasculature. The objective of this study was to isolate autoreactive T-cells specific for arterial antigens, and to characterize these cellsDesign:The presence of autoreactive T-cells in the SHR has not been studied previously. Lymphocytes were isolated from spleens obtained from SHR and Wistar-Kyoto (WKY) rats aged 4, 8, 12,16, 20, 24 and 28 weeksMethods:Limiting dilution analysis was used to clone and to establish arterial antigen-reactive T-cell clones. The specificity of these clones was assessed by measuring lymphokine production and T-cell proliferation induced by arterial antigen and by irrelevant control antigensResults:All of the SHR, regardless of age, possessed arterial antigen-specific CD4+, major histocompatability complex class ll-restricted T-cells. The responses of freshly isolated spleen cells to arterial antigen were weaker than the proliferative responses of interleukin-2-expanded T-cells to arterial antigen. The T-cell clones also produced interleukin-2, interleukin-4 and interferon-γ in response to arterial antigen. However, the presence of T-cells specific for arterial antigen is not unique to SHR, since a similar response was seen in normotensive WKY ratsConclusions:The results indicate the existence of T-cells specific for arterial antigen in the spleens of both SHR and WKY rats. Thus, arterial antigen-reactive T-cells cannot be the initial cause of hypertension, but the activation of such autoreactive T-cells might be important in the development of hypertension

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The nature of the muscarinic (M) receptor subtype mediating endothelium-dependent vasodilation was investigated in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR)Design:Characterization of the muscarinic receptor mediating vasodilation and the possible hypertension-induced effects on the nature of this receptor, which have both received little attention in resistance vessels of the SHRMethods:After a methoxamine-induced vasoconstriction, the vessels were dilated with acetyl-β-metacholine (MCh). The MCh-induced vasodilation was analysed by means of the M1-selective antagonist pirenzepine, the M2-selective antagonists AF-DX116 and AQ-RA741 and the M3-selective antagonists 4-DAMP andp-FHHSiD. The potency of these compounds was quantified by means of pA2values. Atropine, a non-selective muscarinic antagonist, was used for comparisonResults:The rank order of potency for the muscarinic receptor antagonists in preparations taken from SHR and WKY rats appears to be atropine>4-DAMP>p-FHHSiD>pirenzepine>AQ-RA 741 >AF-DX116. This rank order corresponds to that found in isolated conduit arteriesConclusions:The pA2values for the various compounds were not significantly different in SHR and WKY rat preparations, indicating that the nature of this receptor is not influenced by hypertension. The high potency of the M3-selective drugs and the weak activity of pirenzepine and the M2-selective antagonists suggest a major role of M3-receptors in the cholinergic vasodilation in the perfused mesenteric vascular bed both in SHR and WKY rat preparations

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective and design:In spontaneously hypertensive rats (SHR) arterial vasodilators do not cause regression and might cause further progression of cardiac hypertrophy. To assess whether these effects extend to the vasculature, and to examine the possible mechanisms involved, cardiac and mesenteric arterial structure was evaluated with respect to changes in cardiac volume load and cardiac and arterial sympathetic activity during long-term (5- and 10-week) treatment of 16-week-old SHR with the arterial vasodilator minoxidil, alone or in combination with the diuretic hydrochlorothiazideResults:Despite causing a persistent decrease in blood pressure in SHR, minoxidil further increased left and right ventricular weights and left ventricular internal diameter. In combination with hydrochlorothiazide, minoxidil caused concentric, rather than eccentric, left ventricular hypertrophy. In the mesenteric arterial bed of SHR, minoxidil increased the lumen of the superior mesenteric artery, and prevented further increases in the medial area of the large and small mesenteric arteries. The increase in lumen size of the superior mesenteric artery by minoxidil was abolished when hydrochlorothiazide was added to the treatment. After 10 weeks' treatment with minoxidil, noradrenaline turnover rates were still significantly increased in the left ventricle but were decreased in the mesenteric arteries in the SHR. Minoxidil increased plasma and blood volumes, the increases being largely prevented by concomitant diuretic treatmentConclusions:We conclude that there are regional differences in the response of the cardiovascular system to minoxidil in SHR. Some of these differences may be related to differences in regional sympathetic activity, whereas volume load appears to play a modulatory role

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To investigate the role of vascular angiotensin II (Ang II) in the vascular thickening of one-kidney, one clip (1-K,1C) hypertensive rats, which show normal plasma renin activityMethods:The type 1 Ang II receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme (ACE) inhibitor delapril (20mg/kg per day), hydralazine (20mg/kg per day) or vehicle were administered to four groups of 1-K,1C rats aged 6-10 weeks. Vehicle was also given to uninephrectomized ratsResults:The aortae of 1-K,1C rats contained significantly higher levels of AngII than those of uninephrectomized rats and showed hypertrophy, but not hyperplasia of their medial smooth muscle cells. Hypertrophy was estimated by immunohistochemical staining of α-actin. Hyperplasia was estimated by DNA content and incorporation of 5-bromo-2'-deoxyuridine. The blood pressure of the 1-K,1C rats was not affected by either TCV-116 or delapril, even at doses sufficient to induce depressor effects in spontaneously hypertensive rats. However, subdepressor doses of TCV-116 and delapril both significantly reduced the a-actin-stained area to 78 and 73%, respectively, of that in the 1-K,1C rats, whereas a depressor dose of hydralazine did not affect the α-actin-stained area. The level of Ang II in the aorta, but not in plasma, was suppressed by delapril but not by hydralazineConclusions:These results suggest strongly that vascular AngII plays a major role in the development of vascular hypertrophy, independently of plasma Ang II, bradykinin and ACE-independent pathways of AngII generation, and in the regulation of blood pressure in this normoreninaemic hypertensive model

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To compare the acute hypotensive effects of various calcium channel modulators in vitamin B6-deficient hypertensive (B6DHT) ratsMethods:Adult male Sprague-Dawley rats were fed a vitamin B6-deficient diet for 7-10 weeks, during which systolic blood pressure (SBP) was measured in the B6DHT and control rats, using tail-cuff plethysmography. The effects of the calcium antagonists nifedipine, verapamil, diltiazem and (-)-202-791 on SBP were determined in conscious B6DHT rats. The effect of the calcium agonist BAY K 8644 on the SBP of rats fed various levels of pyridoxine was also determinedResults:All of the calcium antagonists used were effective in lowering the SBP of the B6DHT rats with the rank order of potency: nifedipine>(-)-202-791>(±)-verapamil >diltiazem. BAY K 8644 elevated the SBP of older rats fed a normal commercially available diet, but had no effect when the vitamin B6content of their diet was increased or removed for a short periodConclusion:Calcium channel function appears to be related to vitamin B6status in the rat

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:In order to elucidate why spontaneously hypertensive rats (SHR) develop larger brain infarcts distal to an arterial occlusion than normotensive Wistar-Kyoto (WKY) rats, we determined the surface and volume densities of cerebral capillaries, and the regional cerebral blood flow distal to an arterial occlusion in SHR and WKY ratsDesign:Occlusion of the middle cerebral artery was chosen because the middle cerebral artery territory is most commonly affected by cerebral infarcts in manMethods:Surface and volume densities of capillaries in the neocortex of the middle cerebral artery territory were measured by stereological techniques on histological sections. Fifteen minutes after ligation of the right middle cerebral artery, regional cerebral blood flow was measured autoradiographically by the [14C]-iodoantipyrine methodResults:The capillary density of the neocortex did not differ between the SHR and WKY rats. The blood flow was significantly lower within the middle cerebral artery territory in the SHR than in the WKY ratsConclusions:The reduced blood flow distal to the occlusion in SHR is probably a consequence of structural adaptation of arterial resistance vessels, rather than being caused by reduced capillary density

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Although platelets from patients with moderate hypertension are abnormally sensitive to agonist-induced aggregation, their sensitivity to antagonists is not known. Nitric oxide (NO) is an endogenous antagonist of platelet function. The objective of this study was to determine whether platelet sensitivity to the inhibitory activity of sodium nitroprusside, a donor of NO, is abnormal in hypertensionDesign and methods:Untreated patients with uncomplicated essential hypertension (mean arterial pressure >120mmHg) were studied. The rise in cytosolic calcium in response to 9,11-deoxy-11α,9α-epoxymethanoprostaglandin F2α(U46619, a thromboxane mimetic) was measured in fura-2-loaded platelets from 20 patients and 15 normotensive healthy subjects. Inhibition by sodium nitroprusside was measured in a further group of 14 patients and 20 normotensive subjectsResults:Basal cytosolic calcium concentration and the rise in this parameter induced by U46619 were significantly greater in platelets from hypertensive patients than in those from normotensive controls. The mean half-maximal inhibitory concentration of nitroprusside to calcium mobilization induced by 3 µmol/l U46619 was 3.1 -fold greater in platelets from hypertensive patients than in those from controls (95% confidence interval 1.6-6.0)Conclusion:The sensitivity of platelets to nitroprusside is reduced in essential hypertension. This reduced sensitivity to NO might influence the risk of arterial thrombosis in hypertensives

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To examine whether endogenous production of the endotheliumderived vasodilator nitric oxide influences blood pressure in healthy humansMethods:After preliminary pilot dose-ranging studies, 3mg/kg NG-monomethyl-l-arginine (l-NMMA), an inhibitor of nitric oxide synthase, and saline placebo were infused intravenously over 5 min to eight healthy subjects in a two-phase, randomized, single-blind crossover study. Blood pressure and cardiac and renal function were measuredResults:Compared with placebo, L-NMMA increased mean arterial pressure by 10%, decreased heart rate by 19%, decreased cardiac index by 25% and increased calculated total peripheral resistance by 46%. Effects were maximal 10-15 min after starting l-NMMA infusion. Urinary sodium and fractional sodium excretions were increased by l-NMMA, but creatinine clearance was unchangedConclusions:Basal generation of nitric oxide influences total peripheral resistance and blood pressure in healthy humans. The natriuresis induced by L-NMMA may be related to the increase in blood pressure, or arise from inhibition of the intrarenal actions of nitric oxide. Any decrease in nitric oxide generation, as has been postulated to occur in essential hypertension, could have substantial effects on blood pressure and tissue blood flow

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID