Low-density lipoproteins inhibit histamine and NaNO2 relaxations of the coronary vasculature and reduce contractile function in isolated rat hearts

Abstract

In the present study we examined the action of native and oxidized low-density lipoproteins (LDL) on coronary vascular and cardiac function and ultrastructure in rat hearts perfused isovolumically in the Langendorff mode. Responses of the coronary resistance vessels to the endothelium-dependent vasodilator, histamine, and the endothelium-independent vasodilator, NaNO2, were measured together with contractile function (rate-pressure product) before and after perfusion for 20 min with native - or oxidized-LDL at a concentration of 100 mu g protein/ml. Ultrastructural damage was assessed via electron microscopy of perfusion-fixed heart specimens. When compared to findings in untreated, control hearts, both native and oxidized LDL significantly reduced the responsiveness of the coronary resistance vessels to histamine and NaNO2, by about 50%. The rate-pressure product was decreased more by oxidized-LDL (41%) than by native-LDL (26%). Electron microscopy showed no ultrastructural abnormalities in the vasculature or myocytes of control hearts. The administration of both native- and oxidized-LDL caused distortion of endothelial cells, increased levels of pinocytotic vesicles in both endothelial and smooth muscle cells, detachment of blood vessels from surrounding tissue, and some regions of myocyte injury with evidence of mitochondrial injury and fluid accumulation. Our results show that both native- and oxidized-LDL are toxic to the isolated heart preparation. They inhibit coronary vascular responsiveness to vasodilators, reduce contractile function, and produce damage to cardiac ultrastructure.

Novel relationship of serum cholesterol with asthma and wheeze in the United States

“…LDL suppresses cellular responsiveness to TGF-β, 38 a pivotal asthma mediator, inhibits histamine release from human lung mast cells, 39 and inhibits histamine effect. 40 In mice, dyslipidemia is associated with dampened airway inflammation (M. Fessler, unpublished observations). However, whether LDL was causal in the present study or was a marker of other causal mediators such as oxidized LDL is uncertain.…”

LOX-1/LOXIN: The Yin/Yang of Atheroscleorosis

“…Firstly, ox-LDL is present in the atherosclerotic tissues of rupture-prone segments [8]; secondly, the degree of myocardial ischemia is characterized by the oxidative state, which facilitates the oxidation of native-LDL [8] and, thirdly, an in vitro study showed that perfusion with ox-LDL significantly decreases myocardial contraction in isolated rat heart [21]. Moreover, a marked upregulation of LOX-1 was observed in the myocardium of Sprague Dawley rats subjected to coronary artery occlusion for 1 h and reperfusion for 1 h. Most importantly, treatment of rats with a specific antibody to LOX-1 before ischemia reduced LOX-1 expression and prevented myocardial injury, apoptosis and dysfunction [22].…”

Asthma and Obesity in Children

“…A study on the National Health and Nutrition Examination Survey American population found a negative correlation of the total cholesterol and non-HDLs with current asthma only in the Mexican American group [ 83 ]. Several cellular and animal models demonstrated that LDL molecules are taken up by lung cells [ 84 ], where they suppress cellular responsiveness to TGF-β and inhibit histamine release from human lung mast cells and its effect [ 85 , 86 , 87 ]. This physiologic mechanism might explain the protective role of lipids on lung function at least in a selected subgroup of individuals.…”