Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins

Under resting conditions the arterial vasculature exists in a vasoconstricted state referred to as vascular tone. Physiological dilatation in response to increased flow, a function of normal endothelium is necessary to maintain normal blood pressure. Endothelial dysfunction in vascular smooth muscle cells thus results in loss of normal vasorelaxant function and the inability of arteries to appropriately dilate in response to increased blood flow in either a systemic or regional vascular bed, resulting in increased blood pressure, a sequence that may represent a common pathway to hypertension. Normal vasorelaxation is mediated by a number of endothelial systems including nitric oxide (NO), prostaglandins (PGI2 and PGE2), and a family of endothelial-derived hyperpolarizing factors (EDHF). In response to hemodynamic shear stress, endothelium continuously releases NO, EDHF, and PGI2 to provide vasodilatation. EDHF, not a single molecule but rather a group of molecules that includes epoxyeicosatrienoic acids, hydrogen peroxide, carbon monoxide, hydrogen sulfide, C-natriuretic peptide, and K+ itself, causes vasodilatation by activation of vascular smooth muscle cell K+ channels, resulting in hyperpolarization and thus vasorelaxation. The understanding and effective management of blood pressure requires an understanding of both physiologic and pathophysiologic regulation of vascular tone. This review describes molecular mechanisms underlying normal endothelial regulation and pathological states, such as increased oxidative stress, which cause loss of vasorelaxation. Possible pharmacological interventions to restore normal function are suggested.     

Effect of Bioactive Polypeptides on Leaking Large Bowel Anastomosis and Intestines in the Rat

Anastomotic leakage and postoperative adhesions represent major complications after colorectal surgery. We have previously shown a positive effect on both anastomotic strength and abdominal adhesions by the use of differently charged bioactive polypeptides. The present study aimed to investigate the effect of the same polypeptides on the healing of an insufficient intestinal anastomosis, as well as on accidental intestinal injury, in addition to measuring the preventive effect against the development of abdominal adhesions. An insufficient, and thereby potentially leaking, intestinal anastomosis and punctures of the intestine (“accidental intestinal injury model”) were performed in rats. The treatment groups received intraperitoneal administration of poly-L-lysine and poly-L-glutamate, while controls received sodium chloride. Burst pressure, extent of abdominal adhesions, and postoperative complications were analyzed in both experimental models. A significant decrease of adhesions was seen in all animals treated with polypeptides (p <. 05). Burst pressure was significantly higher (p <. 001) in animals with intestinal perforation as seen on day 1 and then decreasing. A significant decrease in the incidence of peritonitis was also noted early (day 1) in this model (p =. 002). The mortality and complications were high in the intestinal anastomosis model, though not affected by treatment with polypeptides. Intraabdominal adhesions were significantly reduced using polypeptides in this study, with no observed effect on other postsurgical complications. There were signs of less infectious complications in polypeptide treated animals. In animals with accidental intestinal injury, a higher burst pressure was noted in treated animals.     

MYO9B gene polymorphisms are associated with autoimmune diseases in Spanish population

The aim of the study was to test MYO9B gene polymorphisms for association with three autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and celiac disease (CD), in a Spanish population. We analyzed three SNPs (rs2305767, rs1457092, and rs2305764) in a case-control cohort composed of 349 SLE patients, 356 RA patients, 90 CD patients, and 345 healthy controls. All three SNPs showed a consistent increased frequency of the A allele in SLE, RA, and CD patients compared with healthy controls. An association was observed between CD and rs2305764 (p=0.01, OR=2.3), between SLE and rs1457092 (p=0.002, OR=1.4), and between RA and rs1457092 (p=0.02, OR=1.3). The three autoimmune diseases combined showed significant association with rs1457092 and rs2305764 and with the AAA haplotype (p haplotype=0.005, OR=1.3). Our data demonstrate consistent association with the A allele and AAA haplotype of three SNPs in the MYO9B gene, which were previously reported to be associated with CD in the Dutch population. This suggests that genetic variation in MYO9B is associated with CD, SLE, and RA and that MYO9B is a general risk factor for autoimmunity.