Cardiovascular effects of endothelin 1 in pithed spontaneously hypertensive rats: evaluation of its mechanism(s) of action

Summary The present experiments were carried out to investigate the cardiovascular effects of endothelin 1 (ET) in pithed spontaneously hypertensive (SH) rats and to evaluate its mechanism of action. The results show that ET (0.1 – 3 nmol/kg i.v.) is a powerful vasoconstrictor agent in the pithed rat. However, at a dose of 3 nmol/kg i.v. all the pithed animals died following a gradual decrease in mean arterial blood pressure and pulse pressure and changes in the form of the electrocardiogram (ECG). The predominant feature of the change in the ECG was a progressive decrease in the amplitude of the T wave resulting in a depression of the curve representing repolarization. Investigations in isolated perfused SH rat hearts showed that ET powerfully reduces coronary flow concentration-dependently (IC₅₀ 2.1 ±0.3 nM) an effect associated with sinus bradycardia and a decrease in coronary pressure amplitude. No overt ECG changes were seen. Control experiments with mechanical flow restriction suggest that bradycardia is a consequence of reduced coronary flow and that the ECG changes observed in vivo can be explained on the basis of coronary insufficiency and resulting myocardial hypoxia. Vasoconstrictor responses to angiotensin II (0.4 g/kg i.v.), phenylephrine (8 g/kg i.v.) and ET (0.5 nmol/kg i.v.) were antagonised by around 70% by isradipine (0.03 mg/kg i.a.). The results suggest that endothelin-induced vasoconstriction may involve receptor operated channel activation and opening of voltage sensitive Ca²⁺ channels.Send offprint requests to A. K. Mir at the above address     

Interaction between clonidine and physostigmine in normal rats and in rats after sinoaortic denervation

Summary Clonidine (3–30 g · kg^–1, i.v.) induced a fall in mean arterial pressure in rats after sinoaortic denervation but not in sham-operated animals. Moreover, sinoaortic denervation reduced the bradycardic action of this antihypertensive drug. Pressor and tachycardic response to physostigmine (60 g · kg^–1, i.v.) were greater in denervated than in sham-operated rats. The increase of mean arterial pressure was 26.2 ± 2.2 mm Hg in sham-operated rats (n = 12) and 53.8 ± 2.0 mm Hg in denervated rats (n = 12, P < 0.005).Pretreatment with 3 g · kg^–1 (i. v.) of clonidine did not alter the pressor response to physostigmine (60 g · kg^–1) in either of the two groups; 10 and 30 g · kg^–1 of clonidine reduced the physostigmine-induced increase of mean arterial pressure in sham-operated rats but enhanced the pressor response in denervated animals. Furthermore, an ineffective dose of physostigmine (30 g - kg^–1 i.v.) induced a pressor response after pretreatment with clonidine (10 gg · kg^–1) in denervated rats.Clonidine (10 g · kg^–1) did not affect the pressor effect of 1,1 dimethyl-4-phenylpiperazinium iodide (DMPP: 50 g · kg^–1 i.v.) or phenylephrine (4 g · kg ^–1, i.v.) in either group.The anticholinergic effect of clonidine in sham-operated rats may be explained by an inhibitory action on the release of acetylcholine in several brain structures but the facilitatory effect of clonidine observed in denervated animals is not clear. The results did not suggest a peripheral involvement in this facilitatory effect. Send offprint requests to M. A. Enero at the above address     

Role of histamine receptor in mesencephalic nucleus dorsalis raphe in cardiovascular regulation

Summary The effects of microinjection of histamine and its antagonists into mesencephalic nucleus dorsalis raphe, were investigated on mean arterial pressure and heart rate in cats to elucidate the nature and role of histaminergic receptors in cardiovascular regulation. Microinjection of histamine (5 and 10 g) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively. On the other hand, microinjection of H₂-receptor blocker, cimetidine (10 g) resulted in hypertension and tachycardia while H₁-receptor antagonist, mepyramine (10 g) microinjection evoked hypotension and bradycardia. Furthermore, local pretreatment with cimetidine and mepyramine blocked the inhibitory and excitatory cardiovascular responses of graded doses of histamine microinjection. These H₁ and H₂ receptors are localized in nucleus dorsalis raphe since microinjection of histamine into adjoining neural structures did not evoke any cardiovascular change. Furthermore, both the inhibitory and excitatory cardiovascular responses to histamine microinjection could not be observed in animals with spinal cord transection and in animals pretreated with p-chlorophenylalanine while they could be observed in bilateral cervical vagotomized animals. Thus, it appears that these cardiovascular responses to microinjection of histamine into nucleus dorsalis raphe, are due to modulation of serotonergic bulbospinal influence on sympathetic preganglionic neurones in the spinal cord. Moreover, the excitatory cardiovascular responses of high dose of histamine (10 g) seem to result from a local release of noradrenaline since they were blocked by prior microinjection of guanethidine and piperoxan into nucleus dorsalis raphe. A release of noradrenaline in turn, modulates the activity of the neurones of the nucleus by acting on adrenoceptors and thereby alters the activity of sympathetic preganglionic neurones. These adrenoceptors appear to be of ₁ type (Saxena et al. 1985, 1987) since phenylephrine microinjection evoked excitatory cardiovascular responses could be blocked by piperoxan. Send offprint requests to K. K. Tangri at the above address     

妊高征患者红细胞免疫粘附调节因子活性的测定

目的 :通过测定妊高征 (PIH)患者红细胞免疫粘附 (RCIA)调节因子活性 ,探讨PIH患者红细胞免疫功能改变的原因。方法 :测定 40例PIH患者和 30例正常孕妇的RCIA促进因子活性和抑制因子活性及红细胞补体受体花环率(RBCC3bRR% )、红细胞免疫复合物花环率 (RBCICR % )。结果 :与正常孕妇相比 ,PIH患者RCIA抑制因子活性明显升高 ,RBCC3bRR%及RBCICR %明显降低 (P <0 .0 1) ,RCIA促进因子活性无明显变化 (P >0 .0 5 )。结论 :PIH患者红细胞免疫功能原发低下 ,其原因可能与RCIA抑制因子活性增高有关     

Diagnostik kardiovaskulärer Erkrankungen mit Hilfe der suprasternalen M-mode Echokardiographie

Summary The suprasternal approach can be used to image the aortic arch, the right pulmonary artery and the left atrium. Dilatation or dissections involving the aortic arch were detected echocardiographically from the suprasternal notch. The echocardiogram of the right pulmonary artery is altered in cases of acute and chronic pulmonary hypertension. Intrapulmonary thrombi in patients with acute pulmonary embolism were visualized with this technique. A volume overloading of the pulmonary circulation due to a congenital left to right shunt, as well as a decreased pulmonary blood flow due to a congenital right to left shunt causes characteristic changes in the wall motion pattern of the right pulmonary artery. Hypoplasia or aplasia of the central pulmonary arteries can be diagnosed as well. Imaging of the left atrium from the suprasternal notch may help to differentiate between supraventricular and ventricular rhythm disturbances. The suprasternal approach is therefore recommended to be used as a routine part of each echocardiographic examination.

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Abkürzungen AO_d enddiastolischer Diameter der Aorta - AO_s mittsystolischer Diameter der Aorta - ASD Vorhofseptumdefekt - AO Aorta - DCM dilative Kardiomyopathie - F₄ Fallot'sche Tetralogie - LA linker Vorhof - NP Normalperson - PH pulmonale Hypertonie - PI Pulmonalinsuffizienz - PSE_AO prozentuale systolische Erweiterung der Aorta - PSE_RPA prozentuale systolische Erweiterung der rechten Pulmonalarterie - PAD_m mittlerer Pulmonalarteriendruck - PC praecordial - Q_RPA maximale Zunahme der Querschnittsfläche der rechten Pulmonalarterie während der Systole - RPA_d end-diastolischer Diameter der rechten Pulmonalarterie - RPA_s mittsystolischer Diameter der rechten Pulmonalarterie - SS suprasternal - SX subxiphoidal Teile der Arbeit wurden durch das BMFT-Projekt 01ZSO31-ZA/NT02 gefördert     

Comparison of Discrete Cardiovascular Fitness Groups on Plasma Catecholamine and Selected Behavioral Responses to Psychological Stress

Discrete cardiovascular fitness groups consisting of high-fit (n=10) and low-fit (n=9) men performed a well-learned vigilance task and their self-report, performance, and plasma catecholamine responses were compared. No significant differences were observed between the fitness groups on self-report or psychomotor performance responses to the vigilance task. However, the low-fit group took significantly longer than high-fit subjects to complete the first of three sets of anagrams administered immediately after the vigilance task. Plasma norepinephrine but not epinephrine response was greater in the low-fit group compared to their high-fit counterparts. The findings indicate that enhanced cardiovascular fitness may be characterized by an attenuated plasma norepinephrine response to a vigilance task with sustained cognitive performance subsequent to the task.     

Defensive hostility and anger expression: Relationship to additional heart rate reactivity during active coping

The main purpose of the present study was twofold: (a) to assess the relationship between defensive hostility (high hostility/high defensiveness) and additional heart rate reactivity during active coping and (b) to determine if the construct of anger-out might lend additional, sensitivity to the predictive power of the defensive hostility model. Forty individuals were randomly assigned to complete a mental arithmetic task with or without the threat of shock. Participants also completed the Cook-Medley Hostility Inventory (Ho), the Marlowe-Crowne Social Desirability Scale (MC), and the Spielberger Anger Expression Scale. Defensive hostile subjects (high Ho/high MC) were significantly more reactive than any other subgroup. In addition, the combination of low Ho/high anger-out scores yielded a subgroup significantly less reactive than any other subgroup. These findings clarify the complex relationship of hostility and cardiovascular reactivity.     

PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study

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Does Low FEV1 in Addition to Fixed Ratio and/or Lower Limit of Normal of FEV1/FVC Improve Prediction of Mortality in COPD? The NHANES-III-linked-mortality Cohort

Purpose

There is presently an ongoing debate on the relative merits of suggested criteria for spirometric airway obstruction. This study tests the null hypothesis that no superiority exists with the use of fixed ratio (FR) of forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) < 0.7 versus less than lower limit predicted (LLN) criteria with or without FEV1 <80% predicted in regards to future mortality.