Biomedical subjects

Maria J Crespo

Publications and source records attributed to Maria J Crespo.

5 recordsLinked to original sources

PubMed2006

Differential regulation of the left and right coronary arteries of swine.

Coronary artery disease is one of the leading causes of myocardial infarction. Despite the predominant role of the coronary arteries in the induction of myocardial infarction, the precise contribution of each artery to this process is not well established. The present work evaluates the histological characteristics and functional properties of the left (LCA) and right (RCA) coronary arteries in swine in order to establish if the arteries are differentially regulated. To investigate this possibility, concentration-response curves for serotonin (5-HT, from 0.1 nmol/l to 100 micromol/l) and KCl (from 5 to 40 mmol/l) were performed on both arteries to determine the receptor-dependent and independent responses, respectively. The specific subtype of the 5-HT receptor involved in the contraction of both arteries was evaluated using DL-propranolol hydrochloride (5-HT1 and nonselective beta-adrenergic receptor antagonist) and ketanserine (5-HT2 antagonist) and immunohistochemical assays. The Emax from the 5-HT concentration-response curves was 24% higher in the LCA than in the RCA (n = 59, p < 0.05). EC50 values from both curves were also significantly different (LCA 0.150 +/- 0.005 micromol/l and RCA 0.171 +/- 0.010 micromol/l, n = 59, p < 0.05). Similarly, the Emax for KCl was 36% higher in the LCA than in the RCA (n = 9, p < 0.05), and the EC50 values also differed (LCA 15.30 +/- 0.06 mmol/l and RCA: 14.30 +/- 0.11 mol/l, n = 9, p < 0.05). Ketanserine reduced the Emax by 63% in the LCA and by 67% in the RCA. DL-propranolol hydrochloride decreased Emax by 24% in the LCA and by 26% in the RCA. The dry weight and media area were larger in the LCA than in the RCA (17%, n = 40, p < 0.05, and 3%, n = 40, p < 0.05, respectively). Immunohistochemical assay results reveal that the average density of 5-HT2A receptor subtype was also higher in the LCA (41.24 +/- 1.35) than in the RCA (18.49 +/- 1.14; n = 20, p < 0.05). Together, the findings of this study suggest that a differential physiological regulation exists between the LCA and RCA in swine. This differential regulation may have arisen as a mechanism for maintaining an adequate perfusion pressure in the wall of the left ventricle, favoring a greater oxygen delivery to match the increased oxygen demand of the left ventricle.

Animals↗

PubMed2006

Increased vascular angiotensin II binding capacity and ET-1 release in young cardiomyopathic hamsters.

Heart failure (HF) is a multifactorial and progressive disease that has been associated with multiple systemic and vascular alterations. Previous reports from our laboratory showed that in 2-month-old Bio-To2 Syrian cardiomyopathic hamsters (SCH) that have not yet developed the clinical manifestations of HF, the vascular contractility induced by 0.1 microM angiotensin II was approximately 35% greater than in control animals. This finding was observed concomitantly with an increased aortic ACE activity. To further evaluate the mechanisms underlying angiotensin II-enhanced vascular contraction, concentration-response curves for angiotensin II (0.01 nM-10 microM) were constructed before and after the addition of prazosin (alpha-1 blocker), NS-398 (selective COX-2 blocker) and BQ-123 (ET-1A-receptor antagonist) in aortic rings from 2-month-old SCH. The binding capacity and affinity of the AT-1 receptors were also evaluated in aortic homogenates using 125I-angiotensin II. Age-matched golden hamsters were used as controls (CT). Our results indicate that incubation with either 10 microM prazosin or 10 microM NS-398 did not modify EC50 or Emax values for angiotensin II indicating that norepinephrine and prostaglandins are not involved in the enhanced contractile action of angiotensin II. However, 10 microM BQ-123 reduced by 40% the contraction induced by 1.0 microM angiotensin II (from 1.05+/-0.04 to 0.6475+/-0.06 g/mg tissue, n = 5, P < 0.05), suggesting that in cardiomyopathic hamsters, the action of angiotensin II is mediated in part by ET-1. At lower angiotensin II concentration (0.1 microM), the ET-1-dependent contraction decreases to 29%. In addition, although dissociation constants for labeled angiotensin II were found to be similar in the aorta of SCH and control animals (K(D): CT = 7.8 nM and SCH = 5.1 nM), 125I-angiotensin II binding capacity was about 2-fold greater in SCH than in controls (Bmax: SCH = 1113 and CT = 605 fmol/mg protein). Altogether these results suggest that in 2-month-old SCH the enhanced response of angiotensin II in the vasculature is mediated both by an increased binding capacity for the hormone and facilitation of the ET-1 action.

Angiotensin II↗

PubMed2006

Statins decrease serotonin-induced contractions in coronary arteries of swine in vitro.

Recent evidence suggests that statins improve the status of patients with coronary artery disease not only by reducing cholesterol levels, but also by acting at the level of the endothelium-smooth muscle unit. Previous results from our laboratory showed that these drugs interact with the vascular wall by partially inhibiting calcium-dependent, agonist-induced contractions in rat aortas. To evaluate whether this effect is also extended to the coronary vasculature, we assessed the effect of statins on serotonin (5-HT) induced contractions of left and right coronary arteries of swine. Concentration-response curves for the 5-HT-induced contractions (from 0.1 nmol/l to 100 micromol/l) were calculated on rings from both coronaries in the presence and absence of either (5 micromol/l) pravastatin, mevastatin, simvastatin, lovastatin, or atorvastatin. After a 45-min incubation period, all statins significantly reduced the Emax for the 5-HT-induced contractions, ranging from 51.9 +/- 1.9% (simvastatin) to 15.9 +/- 2.0% (pravastatin) in the left coronary artery and from 48.8 +/- 2.0% (simvastatin) to 17.8 +/- 2.5% (pravastatin) in the right coronary artery. The EC50 values for the 5-HT-induced contractions were 0.150 +/- 0.005 micromol/l for the left coronary artery and 0.171 +/- 0.010 micromol/l for the right coronary artery. These values significantly changed after incubation with statins, ranging from 1.240 +/- 0.101 micromol/l (for simvastatin) to 0.081+/- 0.008 micromol/l (for pravastatin) in the left coronary artery and from 1.410 +/- 0.075 micromol/l (for simvastatin) to 0.084 +/- 0.008 micromol/l (for pravastatin) in the right coronary artery. This evidence supports the possibility that, beyond their lipid-lowering properties, statins may provide a beneficial effect in atherosclerotic patients by reducing the tone in the coronary vasculature, facilitating blood flow to the myocardium.

Animals↗

PubMed2005

Plasma nitric oxide levels used as an indicator of doxorubicin-induced cardiotoxicity in rats.

INTRODUCTION: The clinical efficacy of doxorubicin is severely limited by its cardiotoxicity. The currently noninvasive techniques used to detect this complication lack sensitivity to identify its early stages. Nitric oxide (NO) is a free radical that has been implicated in the etiology of doxorubicin-induced cardiotoxicity. In the present study, we investigated whether plasmatic NO levels can be used as a noninvasive and reliable biomarker of doxorubicin-induced cardiotoxicity. MATERIALS AND METHODS: Two groups of six spontaneously hypertensive rats (SHR) were used for the experiment. Group 1 received 1.5 mg/kg intraperitoneal (IP) doxorubicin weekly for up to 9 weeks. Group 2 (Control) received nine weekly IP injection of 0.5 cm3 saline. Plasmatic NO levels and cardiac ejection fraction (EF%) were determined. Ventricular biopsies were analyzed by light microscopy according with the Billinghan score. RESULTS: Doxorubicin treatment significantly increased plasmatic NO concentration (35.30+/-5.63 microM versus 14.72+/-2.66 microM in control animals, n=6, P<0.05). In addition, doxorubicin decreased EF by 23% approximately (from 77.00+/-3.89 in controls, to 59.00+/-5.61 in doxorubicin-treated animals, n=6, P<0.05). The mean score of histological cardiac damage was 2.33+/-0.33 for doxorubicin-treated versus 0.08+/-0.08 for controls, n=6, P<0.001. DISCUSSION: Our results revealed a correlation between plasmatic NO levels, systolic function and histopathological myocardial damage. Therefore, it is plausible to postulate that plasmatic NO levels could be used as a biomarker for myocardial damage in doxorubicin-treated SHR, and may be a potential tool for noninvasive evaluation of doxorubicin-induced toxicity in humans.

Animals↗

PubMed2005

Oxidative-nitrosative stress in hypertension.

Reactive oxygen species (ROS) are important signaling molecules in the vasculature. However, when there is imbalance between their occurrence and antioxidant defense mechanisms, ROS can contribute to the vascular abnormalities that lead to hypertension. Evidence accumulated in the last decade strongly supports the notion that ROS are generated in the vasculature mainly by NAD(P)H oxidase in a mechanism that is angiotensin II-dependent. Activation of this enzyme leads to superoxide production and uncouples endothedial NO synthase (eNOS), which sustains oxidative stress while increasing the levels of tissue-damaging peroxynitrite. The latter can result in vascular dysfunction. NAD(P)H-dependent ROS formation, in particular H(2)O(2), could also contribute to vascular injury by sustaining NAD(P)H oxidase activation, promoting inflammatory gene expression, extracellular matrix reorganization, and growth (hypertrophy/hyperplasia) of vascular smooth muscle cells. The effect of ROS appears to be mediated by redox-sensitive targets such as tyrosine kinases and phosphatases, mitogen-activated protein kinases, transcription factors, matrix metalloproteinases, peroxisome proliferator activated receptor-alpha, poly(ADP-ribose)polymerase-1, Ca(2+) signaling mechanisms and secreted factors such as cyclophilin A and heat shock protein 90-alpha. Redox-sensitive targets appear to play a central role in normal vascular function, but can also lead to remodeling of the vascular wall, increasing vascular reactivity and hypertension. Polymorphisms in the p22phox gene promoter could determine susceptibility to NAD(P)H-mediated oxidative stress in humans and animals with hypertension. Although ROS are strongly implicated in the etiology of hypertension, clinical trials with antioxidants are inconclusive regarding their effectiveness in treating the disease. New drugs with both antihypertensive action and antioxidant properties (Celiprolol, Carvedilol) offer promising results in the management of hypertension.

Angiotensin II↗