Activation of vascular endothelial nitric oxide synthase and heme oxygenase-1 expression by electrophilic nitro-fatty acids

Transient reduction in coronary perfusion pressure in the isolated mouse heart increases microvascular resistance (paradoxical vasoconstriction) by an endothelium-mediated mechanism. To assess the presence and extent of paradoxical vasoconstriction in hearts from normal and diabetic rats and to determine whether increased heme oxygenase (HO)-1 expression and HO activity, using cobalt protoporphyrin (CoPP), attenuates coronary microvascular response, male Wistar rats were rendered diabetic with nicotinamide/streptozotocin for 2 wk and either CoPP or vehicle was administered by intraperitoneal injection weekly for 3 wk (0.5 mg/100 g body wt). The isolated beating nonworking heart was submitted to transient low perfusion pressure (20 mmHg), and coronary resistance (CR) was measured. During low perfusion pressure, CR increased and was associated with increased lactate release. In diabetic rats, CR was higher, HO-1 expression and endothelial nitric oxide synthase were downregulated, and inducible nitric oxide synthase and O2− were upregulated. After 3 wk of CoPP treatment, HO activity was significantly increased in the heart. Upregulation of HO-1 expression and HO activity by CoPP resulted in the abolition of paradoxical vasoconstriction and a reduction in oxidative ischemic damage. In addition, there was a marked increase in serum adiponectin. Elevated HO-1 expression was associated with increased expression of cardiac endothelial nitric oxide synthase, B-cell leukemia/lymphoma extra long, and phospho activator protein kinase levels and decreased levels of inducible nitric oxide synthase and malondialdehyde. These results suggest a critical role for HO-1 in microvascular tone control and myocardial protection during ischemia in both normal and mildly diabetic rats through the modulation of constitutive and inducible nitric oxide synthase expression and activity, and an increase in serum adiponectin.

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Endothelial Dysfunction in Breast Cancer In-Vivo Model

Proceedings ◽

10.3390/proceedings2251536 ◽

2018 ◽

Vol 2 (25) ◽

pp. 1536

Author(s):

Buğra Elkar ◽

Mustafa Barış ◽

Meryem Çalışır ◽

Yasemin Çakır ◽

Safiye Aktaş ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Dysfunction ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Growth Factor Receptor ◽

Vascular Endothelial ◽

Vascular Endothelial Cadherin ◽

Oxide Synthase ◽

Endothelial Growth Factor ◽

Endothelial Nitric Oxide

Although the endothelial dysfunction is related with tumor development, there is no consensus on the suppressive or supportive effect on tumor growth. The goal of the present study was to evaluate endothelial dysfunction related factors in animal breast cancer model that was developed by administrating endothelial nitric oxide synthase blocking agent, Nitro-L-arginine methyl ester hydrochloride (L-NAME). Endothelial dysfunction related main factors such as nitric oxide synthase, interleukin-6, vascular endothelial growth factor receptor-2 and vascular endothelial cadherin were investigated by immunohistochemically in tumor and carotid artery tissues. In tumor tissues apoptosis was determined by TUNEL assay. The level of endothelin-1 in blood was measured by ELISA. İntima-media thickness of carotid artery was evaluated with Doppler-USG measurements. As a result, in this study it was shown that vascular endothelial growth factor receptor-2, endothelin-1, endothelial nitric oxide synthase, interleukin-6, vascular endothelial cadherin and E-selectin molecules play a role in reducing breast tumor growth based on endothelial dysfunction.

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