Inhaled therapy for the management of perioperative pulmonary hypertension.

Patients with pulmonary hypertension (PH) are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP). Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary‑specific vasodilator, nitric oxide (NO), has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil), NO‑donating drugs (sodium nitroprusside, nitroglycerin, and nitrite), and phosphodiesterase inhibitors (milrinone, sildenafil) may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators.

Design, synthesis and evaluation of antihypertensive activity of novel nitric oxide-releasing N-phenyl-1H-pyrrole derivatives / 中国药学杂志

OBJECTIVE: To synthesize and evaluate of antihypertensive activity of novel nitric oxide-releasing N-phenyl-1H-pyrrole derivatives. METHODS: By connecting key structural elements present in an AT1 receptor antagonist irbesartan with N-phenyl-1H-pyrrole carboxylic acid, a novel AT1 antagonist compound 4 was designed and synthesized, and a series of novel NO-donating derivatives (IN 1-10) were obtained by introducing NO donor. The amount of NO production in vitro of the target compounds were determined by Greiss assay. And the antagonism of Ang II induced vascular contraction assay was used to value the inhibition rate. RESULTS: The antagonism of Ang II induced vascular contraction assay indicated that the novel compound exhibited similar activity as losartan. The NO derivative, compound IN9, found to release the maximum amount of NO during the NO releasing assay, was more potent than the lead compound 4 and positive control losartan. CONCLUSION: These date indicate that the improved activities of these hybrid molecules contribute to the NO donor and the protection ability of NO donor make them promising candidates as antihypertensive agents.

Inhibitory effect of nitric oxide-donating aspirin against prostatic cancer angiogenesis in tumor-bearing mice / 第二军医大学学报

Objective: To study the inhibitory effect of nitric oxide-donating aspirin(NO-ASA) on prostatic cancer growth and angiogenesis in subcutaneously-injected tumor in mice. Methods: The tumor-bearing mice were subcutaneously injected with NO-ASA, and the tumor growth was observed. ELISA was used to assay the expression of VEGF in mouse sera; real-time PCR was used to examine the expression of VEGF mRNA in tumor tissues; immunohistochemistry was used to detect CD34 expression and to quantify the number of microvessels in the tumor; and Hen's egg test chorioallantoic membrane (HET-CAM) was employed to detect the in vitro angiogenesis. Results: NO-ASA inhibited the prostate cancer growth in mice. The expression of VEGF was greatly decreased in the serum and tumor tissues, and CD34 expression was significantly decreased in the tumor tissues compared with the control group (P<0.05, P<0.01). NO-ASA also greatly inhibited the angiogenesis in HET-CAM. Conclusion: NO-ASA can inhibit prostate cancer growth and angiogenesis.