Effects of indapamide on the mechanical properties of the arterial wall in deoxycorticosterone acetate-salt hypertensive rats

An experimental model of "in situ" isolated carotid artery has been used to evaluate the static mechanical properties of the arterial wall in 12-week-old Wistar and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The rats were made hypertensive by left kidney removal, DOCA (50 mg) tablet implantation for 2 weeks, and saline diet (NaCl 9% solution as beverage). Normotensive control rats (n = 24) and DOCA-salt hypertensive rats (n = 24) received indapamide, 10 mg/kg, or placebo by gavage 12 hours and 1 hour before measurements were obtained. The rats were anesthetized (pentobarbital 50 mg/kg), intubated and ventilated, and a midsternal thoracotomy was performed. A first catheter was introduced into the ascending aorta through the right carotid artery. A perivascular ultrasonic flow probe was placed around the ascending aorta and allowing simultaneous recording of the phasic ascending aortic pressure and flow. Systolic and diastolic pressure, cardiac output and heart rate were directly measured. Peripheral resistance and systemic arterial compliance were calculated from hemodynamic records. After hemodynamic measurements, a segment of the left carotid artery was then isolated in vivo and its volume-pressure relationship was recorded before and 30 minutes after total abolition of the vascular muscle tone by local incubation with a potassium cyanide solution (KCN) (100 mg/liter) for pressures ranging from 50 to 175 mm Hg. The carotid compliance (CC) (microliter/mm Hg) was calculated, for every pressure step, as the slope of the volume-pressure curves. Indapamide significantly reduced the arterial pressure in hypertensive rats, and this was related to a marked decrease in total peripheral resistance. Heart rate was not modified by indapamide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different relation between 24-h blood pressure and distensibility at different peripheral arteries. Data from the European Lacidipine Study on Atherosclerosis (ELSA)

INTRODUCTION: The European Lacidipine Study on Atherosclerosis (ELSA) has been planned to investigate the effect of reduction in office and ambulatory blood pressure by lacidipine versus atenolol on carotid artery wall thickness in mild to moderate essential hypertensive patients with no metabolic abnormalities. One prespecified sub-study of ELSA focused on measurements of arterial distensibility in the carotid as well as in the radial artery to determine the relationship of functional arterial properties with office versus ambulatory blood pressure (BP) values as well as the correspondence between functional and structural arterial alterations. METHODS: The sub-study was conducted on 124 patients recruited in four centres (Monza-Milan, Paris, Grenoble and Glasgow). BP was measured both by a mercury sphygmomanometer and by 24-h ambulatory monitoring. Common carotid artery wall thickness was measured by certified sonographers as described in the main study. Common carotid and radial artery distensibility were obtained by echotracking techniques, which allowed to relate changes in arterial diameter with systo-diastolic BP changes. RESULTS: Carotid artery wall distensibility showed (1) a negative correlation with office and more so 24-h average systolic BP (r = -0.45 and -0.58, P < 0.008 and 0.001) but not with office or 24-h diastolic BP) and (2) a negative correlation with the corresponding wall thickness (r = -0.47, P < 0.005). In contrast, at the radial artery level distensibility and thickness showed no correlation with each other and with BP. Carotid (but not radial) artery distensibility also correlated with ambulatory systolic BP variability but the correlation was lost after adjustment for age and mean BP values. CONCLUSION: These data suggest that stiffening of large elastic artery is reflected more by ambulatory than office BP elevations, systolic BP being much more important than diastolic. Alterations of large elastic arteries function is related to structural wall changes. Functional and structural properties of middle-size muscle arteries are independent of BP.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Distribution and molecular analysis of Blastocystis subtypes from gastrointestinal symptomatic and asymptomatic patients in Iran

IntroductionBlastocystis is a common intestinal parasite of human and animal hosts. The parasite has 17 subtypes, and among those at least nine subtypes (ST1-ST9) are found in human hosts.ObjectiveThe aim of the present study was to investigate the presence of different subtypes of Blastocystis spp. among the patients referred to Velayat hospital of Qazvin province, Iran.MethodsOverall, 864 stool samples were examined by using formalin-ethyl acetate concentration method and Trichrome staining. All specimens were cultured in clotted fetal bovine medium. Later, DNA extraction and PCR amplification of 18S ribosomal RNA gene region was conducted and phylogenetic tree constructed.ResultsThe results revealed 7.9% (68/864) of the study population were infected with Blastocystis. Intestinal symptoms were observed in 61% (36/59) of individuals positive for Blastocystis, with abdominal pain in 58% (21/36) of cases which was more frequent than other intestinal signs. No significant relationship was observed among the study variables. By molecular and phylogenetic analysis, three subtypes ST1 (45%), ST2 (30%) and ST3 (23%) of parasite were identified.ConclusionThis study showed ST1 subtype was the predominant subtype among the positive specimens, meanwhile the highest haplotype and nucleotide diversity were clarified in ST3 subtype.     

Predictors of electromechanical dissociation during cardiac arrest

ECG patterns observed during cardiac arrest were analyzed in 261 comatose cardiac arrest survivors. Forty-seven patients (18%) exhibited electromechanical dissociation (EMD) at some point before restoration of stable spontaneous circulation. These patients had a higher mortality (P = .05) and a lower rate of cerebral recovery (P = .01) during the one-year follow-up than study patients who did not exhibit EMD. Patients who developed EMD subsequent to defibrillation had better outcome than patients presenting with EMD. Multivariate analysis revealed that age more than 70 years old (P = .007), pulmonary disease (P less than .001), diabetes (P = .013, in-hospital arrests only), and prearrest hypoxemia (P = .013, outside-hospital arrests only) were independently predictive of the occurrence of EMD. Although the generalizability of these findings is limited, they may offer new clues to the pathophysiology of EMD.     

Influence of age,risk factors,and cardiovascular and renal disease on arterial stiffness: clinical applications

Age is the main clinical determinant of large artery stiffness. Central arteries stiffen progressively with age, whereas peripheral muscular arteries change little with age. A number of clinical studies have analyzed the effects of age on aortic stiffness. Increase of central artery stiffness with age is responsible for earlier wave reflections and changes in pressure wave contours. The stiffening of aorta and other central arteries is a potential risk factor for increased cardiovascular morbidity and mortality. Arterial stiffening with aging is accompanied by an elevation in systolic blood pressure (BP) and pulse pressure (PP). Although arterial stiffening with age is a common situation, it has now been confirmed that older subjects with increased arterial stiffness and elevated PP have higher cardiovascular morbidity and mortality.

Increase in aortic stiffness with age occurs gradually and continuously, similarly for men and women. Cross-sectional studies have shown that aortic and carotid stiffness (evaluated by the pulse wave velocity) increase with age by approximately 10% to 15% during a period of 10 years. Women always have 5% to 10% lower stiffness than men of the same age.

Although large artery stiffness increases with age independently of the presence of cardiovascular risk factors or other associated conditions, the extent of this increase may depend on several environmental or genetic factors. Hypertension may increase arterial stiffness, especially in older subjects. Among other cardiovascular risk factors, diabetes type 1 and 2 accelerates arterial stiffness, whereas the role of dyslipidemia and tobacco smoking is unclear. Arterial stiffness is also present in several cardiovascular and renal diseases. Patients with heart failure, end stage renal disease, and those with atherosclerotic lesions often develop central artery stiffness. Decreased carotid distensibility, increased arterial thickness, and presence of calcifications and plaques often coexist in the same subject. However, relationships between these three alterations of the arterial wall remain to be explored.