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 ...

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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The mental imagery technique appeared to transfer learning from practice to actual surgery better than textbook study.

Objective-Overproduction of reactive oxygen species such as hydrogen peroxide (H 2 O 2 ) has been implicated in various cardiovascular diseases. However, mechanism(s) underlying coronary vascular dysfunction induced by H 2 O 2 is unclear. We studied the effect of H 2 O 2 on dilation of coronary arterioles to endothelium-dependent and endothelium-independent agonists. Methods and Results-Porcine coronary arterioles were isolated and pressurized without flow for in vitro study. All vessels developed basal tone and dilated dose-dependently to activators of nitric oxide (NO) synthase (adenosine and ionomycin), cyclooxygenase (arachidonic acid), and cytochrome P450 monooxygenase (bradykinin). Intraluminal incubation of vessels with H 2 O 2 (100 mol/L, 60 minutes) did not alter basal tone but inhibited vasodilations to adenosine and ionomycin in a manner similar as that by NO synthase inhibitor L-NAME. H 2 O 2 affected neither endothelium-dependent responses to arachidonic acid and bradykinin nor endothelium-independent dilation to sodium nitroprusside. The inhibited adenosine response was not reversed by removal of H 2 O 2 but was restored by excess L-arginine. Inhibition of L-arginine consuming enzyme arginase by ␣-difluoromethylornithine or N -hydroxy-nor-Larginine also restored vasodilation. Administering deferoxamine, an inhibitor of hydroxyl radical production, prevented the H 2 O 2 -induced impairment of vasodilation to adenosine. Western blot and reverse-transcription polymerase chain reaction results indicated that arginase I was upregulated after treating vessels with H 2 O 2 . Key Words: endothelium Ⅲ free radicals Ⅲ hydrogen peroxide Ⅲ nitric oxide R eactive oxygen species (ROS) from mitochondria and other subcellular sources have been regarded as toxic byproducts of metabolism, especially when excessive production of ROS outstrips endogenous antioxidant defense mechanisms. 1 However, ROS are also known to influence the expression of a number of genes and signal transduction pathways 2 and are thought to act as subcellular messengers for certain growth factors. 3 Interestingly, several cardiovascular diseases with diverse etiologies, such as atherosclerosis, 4 hypertension, 5 vascular complications in diabetes, 6 and after ischemia/reperfusion injury 7 are associated with the common hallmarks of increased oxidative stress and endothelial cell dysfunction. 8 Although the molecular basis of endothelial dysfunction is not completely understood, numerous studies point to the reduction of nitric oxide (NO) biosynthesis and/or bioactivity as a major mechanism. 9 However, the underlying cellular mechanisms contributing to the reduction of NO-mediated effects remain unclear. Conclusions-H See page 1931Perfusion of coronary artery with H 2 O 2 has recently been shown to impair vasodilation in response to NO-mediated agonists; 10 however, the studies suggested that endothelial dysfunction caused by H 2 O 2 was not mediated by the disruption of arginine-NO pathway. 11 In fact, NO synthase (NOS) activity and its exp...