Hypertension is associated with endothelial dysfunction and increased cardiovascular risk. Caveolin-1 regulates nitric oxide (NO) signaling by modulating endothelial nitric oxide synthase (eNOS). The purpose of this study was to examine whether HMG-CoA reductase inhibitor improves impaired endothelial function of the aorta in spontaneous hypertensive rat (SHR) and to determine the underlying mechanisms involved. Eight-week-old male SHR were assigned to either a control group (CON, n=11) or a rosuvastatin group (ROS, n=12), rosuvastatin (10 mg/kg/day) administered for eight weeks. Abdominal aortic rings were prepared and responses to acetylcholine (10-9-10-4 M) were determined in vitro. To evaluate the potential role of NO and caveolin-1, we examined the plasma activity of NOx, eNOS, phosphorylated-eNOS and expression of caveolin-1. The relaxation in response to acetylcholine was significantly enhanced in ROS compared to CON. Expression of eNOS RNA was unchanged, whereas NOx level and phosphorylated-eNOS at serine-1177 was increased accompanied with depressed level of caveolin-1 in ROS. We conclude that 3-Hydroxy-3-methylglutaryl Coenzyme-A (HMG-CoA) reductase inhibitor can improve impaired endothelial dysfunction in SHR, and its underlying mechanisms are associated with increased NO production. Furthermore, HMG-CoA reductase inhibitor can activate the eNOS by phosphorylation related to decreased caveolin-1 abundance. These results imply the therapeutic strategies for the high blood pressure-associated endothelial dysfunction through modifying caveolin status.
Acetylcholine/metabolism ; Animals ; Aorta/metabolism/physiopathology ; Blood Pressure/drug effects ; Caveolin 1/*metabolism ; Down-Regulation ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Fluorobenzenes/administration & dosage/*pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*pharmacology ; Hypertension/enzymology/metabolism/*physiopathology ; Male ; Nitric Oxide/blood ; Nitric Oxide Synthase Type III/*metabolism ; Phosphorylation ; Pyrimidines/administration & dosage/*pharmacology ; Rats ; Rats, Inbred SHR ; Sulfonamides/administration & dosage/*pharmacology ; Vasodilation/drug effects

Pichia ohmeri is a very rare pathogen of human infection. To date, two cases of P. ohmeri infection were reported worldwide. We have experienced a case of catheter-related P. ohmeri fungemia. The patient had been admitted due to cerebrovascular accident in rehabilitation center since August 1998. He had been bedridden due to previous cerebrovascular accident and undergone several episodes of nosocomial infection. Multiple antimicrobial agents had been used with central venous catheter for parenteral nutrition. On February 1999, he had developed fever and dyspnea. Vancomycin and imipenem were administered empirically and central venous catheter was removed on the impression of central venous catheter related infection. Blood culture and catheter tip culture grew P. ohmeri. He developed septic shock and finally led to death before the administration of amphotericin B.
Amphotericin B ; Anti-Infective Agents ; Catheters ; Central Venous Catheters* ; Cross Infection ; Dyspnea ; Fever ; Fungemia* ; Humans ; Imipenem ; Parenteral Nutrition ; Pichia* ; Rehabilitation Centers ; Shock, Septic ; Stroke ; Vancomycin