Abstract-One characteristic of hypertension is a decreased endothelium-dependent nitric oxide (NO)-mediated vasodilation; however, the underlying mechanism is complex. In endothelial cells (ECs), L-arginine is the substrate for both NO synthase (NOS) and arginase. Because arginase has recently been shown to modulate NO-mediated dilation of coronary arterioles by reducing L-arginine availability, we hypothesized that upregulation of vascular arginase in hypertension contributes to decreased NO-mediated vasodilation. To test this hypothesis, hypertension (mean arterial blood pressure Ͼ150 mm Hg) was maintained for 8 weeks in pigs by aortic coarctation. Coronary arterioles from normotensive (NT) and hypertensive (HT) pigs were isolated and pressurized for in vitro study. NT vessels dilated dose-dependently to adenosine (partially mediated by endothelial release of NO) and sodium nitroprusside (endothelium-independent vasodilator). Conversely, HT vessels exhibited reduced dilation to adenosine but dilated normally to sodium nitroprusside. Adenosine-stimulated NO release was increased Ϸ3-fold in NT vessels but was reduced in HT vessels. Moreover, arginase activity was 2-fold higher in HT vessels. Inhibition of arginase activity by N -hydroxynor-L-arginine or incubation with L-arginine partially restored NO release and dilation to adenosine in HT vessels. Immunohistochemistry showed that arginase expression was increased but NOS expression was decreased in arteriolar ECs of HT vessels. These results suggest that NO-mediated dilation of coronary arterioles is inhibited in hypertension by an increase in arginase activity in EC, which limits L-arginine availability to NOS for NO production. The inability of arginase blockade or L-arginine supplementation to completely restore vasodilation may be related to downregulation of endothelial NOS expression. Key Words: arginine Ⅲ hypertension Ⅲ microcirculation Ⅲ nitric oxide synthase Ⅲ vasodilation H ypertension is a major risk factor for coronary artery disease. One characteristic of hypertension that appears to be critical in the development of vascular disease is the impairment of endothelial function. For example, there is a markedly reduced endothelium-dependent vasodilation in both large and small coronary arteries from hypertensive humans and animal models of hypertension. 1 Mounting evidence suggests that this vascular impairment may be related to a diminished production and bioavailability of the potent vasodilator nitric oxide (NO), which may result from an increased vascular production of superoxide anion 2 or decreased endothelial levels of tetrahydrobiopterin 3,4 or L-arginine. 5 Interestingly, administration of NO precursor L-arginine restores endothelium-mediated vasodilatory function in patients with essential hypertension, 5 improves coronary hemodynamics in spontaneously hypertensive rats, 6 and increases NO production and reduces blood pressure in hypertensive rats with 7 or without 8 renal failure. These results suggest the possible reduction of L-arginine ...

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BackgroundPublished information regarding survival and long‐term cardiac remodeling after patent ductus arteriosus (PDA) closure in dogs is limited.ObjectivesTo report outcome and identify prognostic variables in dogs with PDA, and to identify risk factors for persistent remodeling in dogs with a minimum of 12 months of follow‐up after closure.AnimalsFive hundred and twenty client‐owned dogs.MethodsRetrospective review of medical records of 520 dogs with PDA. Outcome was determined by contacting owners and veterinarians. Dogs with PDA closure and ≥ 12 months of follow‐up were asked to return for a re‐evaluation.ResultsIn multivariable analysis of 506 dogs not euthanized at the time of diagnosis, not having a PDA closure procedure negatively affected survival (HzR = 16.9, P < .001). In 444 dogs undergoing successful PDA closure, clinical signs at presentation (HzR = 17, P = .02), concurrent congenital heart disease (HD) (HzR = 4.8, P = .038), and severe mitral regurgitation (MR) documented within 24 hours of closure (HzR = 4.5, P = .028) negatively affected survival. Seventy‐one dogs with ≥ 12 months follow‐up demonstrated a significant reduction in radiographic and echocardiographic measures of heart size (P = 0) and increased incidence of acquired HD (P = .001) at re‐evaluation. Dogs with increased left ventricular size and low fractional shortening at baseline were more likely to have persistent remodeling at re‐evaluation.Conclusions and Clinical ImportancePatent ductus arteriosus closure confers important survival benefits and results in long‐term reverse remodeling in most dogs. Clinical signs at presentation, concurrent congenital HD, and severe MR negatively affect survival. Increased left ventricular systolic dimensions and systolic dysfunction at baseline correlated significantly with persistent remodeling.

Cerebral aneurysms treated by traditional endovascular methods using platinum coils have a tendency to be unstable, either due to chronic inflammation, compaction of coils, or growth of the aneurysm. We propose to use alternate filling methods for the treatment of intracranial aneurysms using polyurethane based shape memory polymer (SMP) foams. SMP polyurethane foams were surgically implanted in a porcine aneurysm model to determine biocompatibility, localized thrombogenicity, and their ability to serve as a stable filler material within an aneurysm. The degree of healing was evaluated via gross observation, histopathology and low vacuum scanning electron microscopy (LV-SEM) imaging after zero, thirty and ninety days. Clotting was initiated within the SMP foam at time zero (less than one hour exposure to blood prior to euthanization), partial healing was observed at thirty days, and almost complete healing had occurred at ninety days in vivo, with minimal inflammatory response.

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