eNOS, Endothelial nitric oxide synthase (eNOS) is the
catalyst of endothelial nitric oxide (NO) synthesis
September 15 2016
Redox Biology 2014. Endothelial nitric oxide synthase in red blood cells: Key to a new erythrocrine function? Red blood cells (RBC) have been considered almost exclusively as a transporter of metabolic gases and nutrients for the tissues. It is an accepted dogma that RBCs take up and inactivate endothelium-derived NO via rapid reaction with oxyhemoglobin to form methemoglobin and nitrate, thereby limiting NO available for vasodilatation. Yet it has also been shown that RBCs not only act as "NO sinks", but exert an erythrocrine function - i.e an endocrine function of RBC - by synthesizing, transporting and releasing NO metabolic products and ATP, thereby potentially controlling systemic NO bioavailability and vascular tone. Recent work from our and others laboratory demonstrated that human RBCs carry an active type 3, endothelial NO synthase (eNOS), constitutively producing NO under normoxic conditions, the activity of which is compromised in patients with coronary artery disease. In this review we aim to discuss the potential role of red cell eNOS in RBC signaling and function, and to critically revise evidence to this date showing a role of non-endothelial circulating eNOS in cardiovascular pathophysiology.
Int J Impot Res. 2013. Effects of chronic treatment with the eNOS stimulator Impaza on penis length and sexual behaviors in rats with a high baseline of sexual activity. Department of Psychology, University of Tromsų, Tromsų, Norway. Endothelial nitric oxide synthase (eNOS) has an important role in erection, and it also affects aspects of sexual behavior. In this experiment, we determined whether a compound enhancing the activity of eNOS, Impaza, could stimulate any aspect of sexual behavior and increase penis length in rats with a high baseline of sexual activity. For comparison, the PDE5 inhibitor sildenafil was included. Male rats were orally treated with Impaza or sildenafil for 28 days. Impaza (3 ml kg-1) was given daily while sildenafil (3 mg kg-1) was given twice weekly. Tests for sexual incentive motivation and copulatory behavior were performed just before drug treatment and at days 7, 14 and 28 of treatment. In addition, the length of the protruding penis at mount, intromission and ejaculation was measured. Impaza but not sildenafil increased penis length at mount after 14 and 28 days of treatment. The compounds failed to modify sexual incentive motivation or copulatory behavior. It is suggested that Impaza enhanced intracavernous pressure, as such a pressure increase is the most likely explanation for enhanced penis length at mount. This effect, together with an absence of motivational actions, suggests that Impaza may be the most valuable treatment for erectile dysfunction. International Journal of Impotence Research advance online publication, 14 March 2013; doi:10.1038/ijir.2013.12.
Int J Impotence Res. 2012. Hydrogen sulfide promotes nitric oxide production in corpus cavernosum by enhancing expression of endothelial nitric oxide synthase. Department of Obstetrics & Gynecology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Recently, hydrogen sulfide (H(2)S) has been identified as a potential therapy for ED. However, a thorough understanding of its molecular mechanisms of action would be essential to develop H(2)S as a new therapy for ED. In this study, the effect of H(2)S on nitric oxide (NO) production, especially through the expression of constitutive nitric oxide synthase (NOS) isoforms-endothelial NOS (eNOS) and neuronal NOS (nNOS) in rat corpus cavernosum (CC) were explored. Real-time PCR studies subsequent to in vitro treatment of sodium hydrosulfide hydrate (NaHS), a stable H(2)S donor, showed increases in eNOS but not nNOS mRNA. Western blot studies confirmed that the exogenously applied NaHS increased eNOS but not nNOS protein expression in the rat CC. Furthermore, NaHS did not alter the expressed amounts of Caveolin-1 (CAV-1), a dominant inhibitory interaction partner of eNOS, in these tissues. Not surprisingly, NaHS also enhanced the NO production in eNOS-associated membrane fraction of rat CC. Taken together, we ascertain that H(2)S could exert its proerectile effects by augmenting NO pathway. It appears that H(2)S would be particularly useful in improving the clinical outcome of ED patients, whose erectile impairment is due to an inherent attenuation of the endothelial NO formation in the cavernosum.