自发性高血压大鼠颈动脉血管平滑肌中抑癌基因P53和原癌基因c-jun、c-fos、c-myc mRNA表达的研究

目的探讨自发性高血压大鼠颈动脉中抑癌基因P53和原癌基因c-jun、c-fos、c-myc mRNA的表达.方法用逆转录聚合酶链式反应检测两种基因的表达水平.正常雄性大鼠作为对照组.结果 SHR颈动脉中,抑癌基因P53和原癌基因c-jun、c-fos、c-myc均有高表达,较WKY差异有显著性(P<0.05).结论自发性高血压大鼠颈动脉组织中抑癌基因P53和原癌基因c-jun、c-fos、c-myc均有高表达,癌基因的活化可能与自发性高血压大鼠颈动脉血管重构有关.     

久强脑立清对自发性高血压大鼠重要器官的保护作用

目的探讨久强脑立清 (JNQ )对自发性高血压大鼠 (SHR)重要器官心、脑、肾组织形态学的影响。方法动物分为 4组 ,Wistar大鼠对照组、SHR组、SHR服用JNQ高剂量组 (0 5 3 0g/kg)和低剂量组 (0 2 65 g/kg) ,给药 5周。采用尾脉搏测压法测定动物血压 ;动物经组织灌流后 ,低温下快速取出心、脑、肾 ,固定于 10 %福尔马林中 ,4℃保存 ,常规组织切片 ,HE染色。结果给药前各组SHR的血压明显高于对照组 (P <0 0 1) ,给药 3周和 5周后血压未见明显下降。组织病理结果显示 ,未治疗组SHR心肌细胞肥大 ,肌束间小动脉壁增厚 ,官腔变窄 ;大脑皮层血管管腔狭窄 ,管壁增厚 ,血管周围间隙增大 ;肾小球萎缩 ,有玻璃样变。上述病理性改变在经JNQ治疗 5周后得到不同程度的改善 ,以高剂量组明显。结论SHR经JNQ治疗 5周后血压未见明显降低 ,但对重要器官心、脑、肾的病变有较明显改善作用     

Characterization of dihydropyridine binding sites in the rat brain: hypertension and age-dependent modulation of [H](+)-PN 200-110 binding

The properties of [³H]dihydropyridine (DHP), nitrendipine and (+)-PN 200-110, binding to rat cerebral membranes were investigated. In normotensive Wistar-Kyoto (WKY) adult rats, the highest densities of [³H]DHP binding sites were found in the hippocampus. Frontal cerebral cortex and hypothalamus had intermediate levels and no specific binding of [³H]DHP and [¹²⁵I]iodipine could be detected in the brainstem membranes and more precisely in the nucleus tractus solitarius and in the locus coeruleus. Changes in the maximal number of DHP binding sites (B_max) were observed in spontaneously hypertensive rats (SHR) and in old Sprague-Dawley rats. In adult SHR, there was a significant increase in theB_max values of [³H](+)-PN 200-110 binding in the hippocampus when compared to the values obtained in WKY. There was no difference in theB_max values between young (3 weeks) prehypertensive SHR and age-matched WKY. In senescent (26 months) Sprague-Dawley rats, theB_max values of [³H](+)-PN 200-110 binding were significantly reduced (30%) in the frontal cerebral cortex and the hippocampus, as compared with the number of DHP binding sites found in mature Sprague-Dawley rats (15 weeks).     

Persistent Hypotension Associated with Hypermedullipinemia: A New Syndrome

A new syndrome is described in a patient with advanced renal insufficiency. This consists of severe and persistent hypotension causing weakness but associated with a clear mental status. Also present is evidence for decreased vascular reactivity. The hypotension was not orthostatic. The hypotension was associated with a circulating vasodepressor substance having the characteristics of medullipin I. The medullipin appears to have been derived from the remaining right kidney. Hypotension existed despite the presence of major prohypertensive mechanisms, including an endstage kidney, hyperreninemia and hyperaldosteronemia. It is likely that hypotension due to hypermedullipinemia is an entity occurring in the human being.     

Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Summary— Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-β-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10⁻⁴M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.     

Permanent brain ischemia induces marked increments in hsp72 expression and local protein synthesis in synapses of the ischemic hemisphere

Transient focal ischemia induced in rat brain by occlusion of the middle cerebral artery (MCAo) elicits a generalized induction of the 72 kDa heat-shock protein (hsp72) heralding functional recovery. As this effect implies activation of protein synthesis, and local systems of protein synthesis are present in brain synapses, and may be analyzed in preparations of brain synaptosomes, we evaluated hsp72 expression and protein synthesis in synaptosomal fractions of spontaneously hypertensive rats (SHRs) subjected to permanent MCAo. SHRs were randomly divided in ischemics and sham controls, anaesthesia controls and passive controls. Focal ischemia was induced under chloral hydrate anaesthesia by unilateral permanent MCAo. Protein synthesis was determined by [³⁵S]methionine incorporation into synaptosomal proteins from ischemic and contralateral cortex/striatum, and from cerebellum. Hsp72 expression was measured in the same fractions by immunoblotting. Our data demonstrate that under these conditions synaptic hsp72 markedly increases in the ischemic hemisphere 1 and 2 days after MCAo, progressively declining in the following 2 days, while no significant change occurs in control rats. In addition, in the ischemic hemisphere the rate of synaptic protein synthesis increases more than two-fold between 1 and 4 days after MCAo, without showing signs of an impending decline. The present data provide the first demonstration that synaptic protein synthesis is massively involved in brain plastic events elicited by permanent focal ischemia.     

Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR): (1) control; (2) calcium; (3) deoxycorticosterone and; (4) deoxycorticosterone + calcium. Calcium was given as 1.5% calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg^-1). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone + calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium-treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone-induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.     

Reflex inhibition of sympathetic activity during volume load in awake normotensive and spontaneously hypertensive rats

The reflex inhibition of the sympathetic activity in the splanchnic nerves was recorded upon volume expansion with blood in awake spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKR) at an age of 16–20 weeks. At 10% blood volume expansion SHR showed a significantly greater nerve inhibition (43 %) in comparison with WKR (33 %). This augmented reflex response was not caused by the arterial baroreceptors, because the sensitivity of the arterial baroreceptor reflex arch, if anything, tended to be lower in SHR and the increase in arterial blood pressure upon volume load was also lower in SHR. It is suggested that the reason for this increased reflex inhibition in SHR is an augmented low pressure receptor response. The mechanism behind this is discussed. The most likely explanation is a decreased distensibility of the venous system, the systemic andlor the pulmonary veins.