Baroreflex control of heart rate in the broad-nosed caiman Caiman latirostris is temperature dependent

It has been suggested that ectothermic vertebrates primarily control blood pressure to protect the pulmonary vasculature from oedema caused by high pressure, while endothermic vertebrates control blood pressure to maintain adequate oxygen delivery to the tissues. In the present study we have characterised how temperature affects the cardiac limb of the baroreflex in the intact unanaesthetized broad-nosed caiman (Caiman latirostris) by pharmacological manipulation of blood pressure in a closed-loop system. Sodium nitroprusside (SNIP) and phenylephrine were used to manipulate arterial pressure and the resulting alterations in heart rate were used to calculate the gain of the baroreflex. Both drugs were infused as bolus injections in concentrations of 5, 10, 25, 50 and 100 mu g kg(-1). The barostatic response was present at both 15 and 30 degrees C, and, at both temperatures, C. latirostris responded to reductions in systemic blood pressure (Psys). At 30 degrees C the baroreflex was more pronounced at a blood pressure lower than control value (52.3 cmH(2)O) with a maximal baroreflex gain of 1.97 beats min(-1) cmH(2)O(-1) at a Psys of 41.9 cmH(2)O, and therefore seems to counteract hypotension. In contrast, the maximal baroreflex at 15 degrees C was found at a Psys almost equal to the control value. The highest baroreflex gain in response to change in blood pressure was measured at the highest temperature. Thus, C. latirostris exhibit a temperature dependent barostatic response. (C) 2010 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Increased retention of LDL from type 1 diabetic patients in atherosclerosis-prone areas of the murine arterial wall

BACKGROUND AND AIMS: Type 1 diabetes accelerates the development of atherosclerotic cardiovascular diseases. Retention of low-density lipoprotein (LDL) in the arterial wall is a causal step in atherogenesis, but it is unknown whether diabetes alters the propensity of LDL for retention. The present study investigated whether LDL from type 1 diabetic and healthy non-diabetic subjects differed in their ability to bind to the arterial wall in a type 1 diabetic mouse model. METHODS: Fluorescently-labeled LDL obtained from type 1 diabetic patients or healthy controls was injected into mice with type 1 diabetes. The amount of retained LDL in the atherosclerosis-prone inner curvature of the aortic arch was quantified by fluorescence microscopy. Healthy control LDL was in vitro glycated, analyzed for protein glycation by LC-MS/MS, and tested for retention propensity. RESULTS: Retention of LDL from type 1 diabetic patients was 4.35-fold higher compared to LDL from nondiabetic subjects. Nuclear magnetic resonance (NMR) spectroscopy analysis of LDL revealed no differences in the concentration of the atherogenic small dense LDL between type 1 diabetic and non-diabetic subjects. In vitro glycation of LDL from a non-diabetic subject increased retention compared to non-glycated LDL. LC-MS/MS revealed four new glycated spots in the protein sequence of ApoB of in vitro glycated LDL. CONCLUSIONS: LDL from type 1 diabetic patients showed increased retention at atherosclerosis-prone sites in the arterial wall of diabetic mice. Glycation of LDL is one modification that may increase retention, but other, yet unknown, mechanisms are also likely to contribute.This work was supported by The Arvid Nilssons Foundation, Fonden til Laegevidenskabens Fremme, Snedkermester Sophus Jacobsen & Hustru Astrid Jacobsens Fond, Laegeforeningen, The Novo Nordisk Foundation, John and Birthe Meyer Foundation, The Danish Council for Independent Research (10-093408) and Danish Diabetes Academy. AGRADECIENTOS

Physiological importance of the coronary arterial blood supply to the rattlesnake heart

The reptilian heart consists of a thick inner spongy myocardium that derives its oxygen and nutrient supply directly from the blood within the ventricular cavity, which is surrounded by a thin outer compact layer supplied by coronary arteries. The functional importance of these coronary arteries remains unknown. In the present study we investigate the effects of permanent coronary artery occlusion in the South American rattlesnake (Crotalus durissus) on the ability to maintain heart rate and blood pressure at rest and during short term activity. We used colored silicone rubber (Microfil) to identify the coronary artery distribution and interarterial anastomoses. The coronary circulation was occluded and the snakes were then kept for 4 days at 30 degrees C. Microfil injections verified that virtually all coronary arteries had successfully been occluded, but also made visible an extensive coronary supply to the outer compact layer in untreated snakes. Electrocardiogram (ECG), blood pressure (P(sys)) and heart rate (f(H)) were measured at rest and during enforced activity at day 1 and 4. Four days after occlusion of the coronary circulation, the snakes could still maintain a P(sys) and f(H) of 5.2 +/- 0.2 kPa and 58.2 +/- 2.2 beats min(-1), respectively, during activity and the ECG was not affected. This was not different from sham-operated snakes. Thus, while the outer compact layer of the rattlesnake heart clearly has an extensive coronary supply, rattlesnakes sustain a high blood pressure and heart rate during activity without coronary artery blood supply

Type 1 diabetes increases retention of low-density lipoprotein in the atherosclerosis-prone area of the murine aorta

BACKGROUND AND AIMS: Individuals with type 1 diabetes mellitus are at high risk of developing atherosclerotic cardiovascular disease, but the underlying mechanisms by which type 1 diabetes accelerates atherosclerosis remain unknown. Increased retention of low-density lipoprotein (LDL) in atherosclerosis-prone sites of the diabetic vascular wall has been suggested, but direct evidence is lacking. In the present study, we investigated whether retention of LDL is increased in atherosclerotic-prone areas using a murine model of type 1 diabetes. METHODS: Fluorescently-labeled human LDL from healthy non-diabetic individuals was injected into diabetic Ins2Akita mice and non-diabetic, wild-type littermates. The amount of retained LDL after 24 h was quantified by fluorescence microscopy of cryosections and by scans of en face preparations. Vascular gene expression in the inner curvature of the aortic arch was analyzed by microarray and quantitative polymerase chain reaction. RESULTS: LDL retention was readily detected in atherosclerosis-prone areas of the aortic arch being located in both intimal and medial layers. Quantitative microscopy revealed 8.1-fold more retained LDL in type 1 diabetic mice compared to wild-type mice. These findings were confirmed in independent experiments using near-infrared scanning of en face preparations of the aorta. Diabetic status did not affect arterial expression of genes known to be involved in LDL retention. CONCLUSIONS: Type 1 diabetes increases the ability of the vascular wall to retain LDL in mice. These changes could contribute to the increased atherosclerotic burden seen in type 1 diabetic patients.This work was supported by The Arvid Nilssons Foundation, Fonden til Laegevidenskabens Fremme, Snedkermester Sophus Jacobsen & Hustru Astrid Jacobsens Fond, Laegeforeningen, The Novo Nordisk Foundation and The Danish Council for Independent Research (10-093408).S

Apolipoprotein E Deficiency Increases Remnant Lipoproteins and Accelerates Progressive Atherosclerosis, But Not Xanthoma Formation, in Gene-Modified Minipigs

Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, APOE was targeted in Yucatan minipigs. APOE−/− minipigs displayed increased plasma cholesterol and accumulation of apolipoprotein B-48–containing chylomicron remnants on low-fat diet, which was significantly accentuated upon feeding a high-fat, high-cholesterol diet. APOE−/− minipigs displayed accelerated progressive atherosclerosis but not xanthoma formation. This indicates that remnant lipoproteinemia does not induce early lesions but is atherogenic in pre-existing atherosclerosis