Heterogeneous distribution of endothelium-dependent relaxations resistant to NG-nitro-L-arginine in rats

Abstract

Endothelium-dependent relaxations that are resistant to inhibitors of nitric oxide synthase probably are mediated by endothelium-dependent hyperpolarization of the vascular smooth muscle. Experiments were performed to examine the distribution of this type of relaxation along the arterial tree of the rat by measuring changes in isometric force. Acetylcholine induced concentration- and endothelium-dependent relaxations in aortas and in pulmonary, common iliac, femoral, mesenteric, and renal arteries contracted with phenylephrine. In the presence of NG-nitro-L-arginine, the cumulative administration of acetylcholine induced relaxations only in the femoral, mesenteric, and renal arteries. The calcium ionophore A23187 relaxed mesenteric arteries contracted with phenylephrine in a concentration- and endothelium-dependent manner. The concentration-relaxation curve to A23187 was shifted to the right in the presence of NG-nitro-L-arginine. The maximal relaxations induced by lemakalim, a K+ channel opener, were smaller in those arteries that did not exhibit NG-nitro-L-arginine-resistant relaxations. These results suggest that NG-nitro-L-arginine-resistant relaxations are more frequently observed in smaller arteries. The arteries that exhibit NG-nitro-L-arginine-resistant relaxations may be more sensitive to an endothelium-derived substance that causes hyperpolarization of vascular smooth muscle cells.

The pathogenesis of diabetic retinopathy: old concepts and new questions

“…EDHF contributes greatly to vascular control of small-diameter vessels and microvessels involved in the local regulation of peripheral vascular resistance and thus in the distribution of blood flow. 40 By contrast, NO and PGI2 are more committed to regulation of large-diameter vessels. A list of potential agents/cellular events which could function as EDHF include eoxyeicosatrienoic acid (EET), [41][42][43][44][45][46] hydrogen peroxide, 47 potassium efflux, 48 and gap junction communication between endothelial cells and smooth muscle cells.…”

The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin - induced diabetic rats is restored by 5-methyltetrahydrofolate

“…The contribution of EDHF to relaxation is dependent on vessel size, being more prominent in smaller, physiologically more important, arteries than in larger ones [2,28]. Hence, we did additional experiments using the split hydronephrotic kidney model, an intravital microscopy technique with which it is possible to examine the different segments of the renal microcirculation in vivo.…”

“…Endothelial integrity is generally assessed by evaluating the vasodilator response of a blood vessel or a vascular bed to an endothelium-dependent agonist [2]. Endothelial cells relax the tone of the underlying vascular smooth muscle cells by releasing a number of vasodi- Diabetologia (2000) Abstract Aims/hypothesis.…”

Asymmetric Dimethylarginine Produces Vascular Lesions in Endothelial Nitric Oxide Synthase–Deficient Mice

“…8,9 This model with L-NAME is regarded as a useful animal model for examining the protective roles of endothelium-derived NO in the pathogenesis of arteriosclerosis. 8,9 See cover However, it is controversial whether these vascular effects of L-NAME are caused primarily by the inhibition of endothelial NO synthesis for the following reasons: first, the importance of endothelium-derived NO decreases as the vessel size becomes smaller, 10 whereas L-NAME-induced vascular lesions are prominent at microvascular levels; 8 second, long-term treatment with L-NAME does not reduce eNOS activity; 11 third, multiple actions of L-NAME other than simple inhibition of NO synthesis have been reported. 12,13 The most appropriate way to address this issue is to use mice that are deficient in the eNOS gene and to examine whether long-term treatment with L-NAME causes coronary vascular lesions in those mice.…”