Primary Arterial Hypertension News - Menu Medical Researchers Say Statins, Other
Cholesterol-Depleting Agents Affect Hypertension By Sue Pondrom April 3, 2005 - Cholesterol-lowering agents, such as the widely-prescribed statin drugs, and cholesterol-blocking agents may prove to be “novel therapeutic agents to modify cellular calcium that contributes to the development of pulmonary hypertension,” according to Hemal H. Patel, who leads a multidisciplinary team of researchers at the UCSD School of Medicine. Presenting his research at the 35th Congress of the International Union of Physiological Sciences on Tuesday, April 5 in San Diego, Patel said the team found a previously unappreciated cellular and molecular mechanism for the disease process in idiopathic pulmonary hypertension (IPAH), which was previously called primary pulmonary hypertension. He added that the mechanism found may be amenable to treatment with current and future therapies and might provide more substantial, long-term and efficacious benefit to those who have IPAH. A severe clinical disease with a poor prognosis, untreated IPHA leads to heart failure and death in two to eight years. Because of limited understanding of the cellular and molecular determinants of the disease process, current therapy is limited and aimed towards symptomatic relief. Patel, who is a post doctoral fellow in the lab of Paul Insel, M.D., UCSD professor of pharmacology, said two factors that contribute to the disease are dependent on cellular calcium: constriction of vessels, and uncontrolled cell growth resulting in thickening of vessels. The UCSD team sought to determine if IPAH has altered caveolae, which in Latin means “little caves,” on the membrane composed of cholesterol that control the intake of calcium into cells. They also wanted to know if agents that modify cellular cholesterol might limit calcium intake and ultimately limit the two factors (constriction and growth) in vessels that contribute to the disease process. These drugs then might provide for a novel therapy that not merely provides temporary relief of disease symptoms, but helps alleviate the underlying cause of IPAH. In their research, the team saw that “smooth muscle cells isolated from pulmonary arteries of patients with IPAH indeed had more caveolae on the cell membrane compared to cells from normal individuals, and also that there was a higher calcium intake into the diseased cells,” Patel reported. Subsequent treatment of the IPAH cells with an agent that depletes cholesterol (methyl-beta-cyclodextrin, or MBCD), or “a statin (in this case, lovostatin, sold as Mevacor by Merck), which blocks cholesterol synthesis, resulted in a disruption of the caveolae and reduced the amount of calcium that entered the cells. “Additionally, these two treatments also decreased the growth rate of the diseased cells,” Patel said. Taken together, the results “mean that the micro-structure of the cell membrane is involved in controlling the intake of calcium and that the cholesterol modifiers of these structures may serve as novel therapeutics to reduce vessel constriction and cell growth associated with increased calcium intake in IPAH,” Patel stated. The next steps, Patel explained, are to understand the nature of the proteins located on the caveolae and how these structures communicate with the internal regions of cells to influence calcium intake into the cell. He said the UCSD researchers “already have begun looking at the expression and localization of ion channels into caveolae that may further explain the increased calcium intake into cell.” In addition to Patel, researchers included Insel and Fiona Murray, Ph.D., UCSD Department of Pharmacology; Shen Zhang, Ph.D. and Jason X-J Yuan, M.D., Ph.D., UCSD Department of Medicine, and Patricia A. Thistlethwaite, M.D., Ph.D., UCSD Department of Surgery. The study was funded by the National Institutes of Health. Contact during the March 31-April 5 Congress:
Mayer Resnick, IUPS/APS newsroom 619-525-6228 or 301-332-4402 (cell) or Stacy Brooks at 240-432-9697 (cell) or 301-634-7253 (office)
UCSD Contact: Sue Pondrom 619-543-6163
Viagra ‘breakthrough’
By A Staff Reporter
MUSCAT — The male potency cure, Viagra, is said to contain a vital ingredient that can be used to treat pulmonary hypertension (PPH), a life-threatening vascular disease.
Experts detailed this key Viagra ‘breakthrough’ to a gathering of leading Omani health practitioners recently.
The PPH is a complex condition, in which high pressure in the blood vessels moves from the heart to the lungs, causing symptoms such as difficulty in breathing, dizziness and fatigue. It can affect people of all ages and genders. The Viagra breakthrough has been hailed as ‘crucial’ by experts as life expectancy for patients once diagnosed with PPH is only two years and eight months.
Dr Mohamed Khalifa of Pfizer, the company which made the discovery, told a gathering of leading Omani doctors: “Viagra has been clinically proven to be a safe and effective impotence cure, after more than 13,000 patient-years of observation in clinical trials — more than any other impotence drug. The news that Viagra can also be used to potentially save lives is great news for PPH sufferers, and also confirms the fact that Viagra is an extremely safe oral therapy. It also underlines Pfizer’s commitment to developing cures for all types of medical disorders.”
In a clinical trial, patients showed ‘significant’ improvement in distance covered during a six-mile walk — a standard measure of efficacy for pulmonary arterial hypertension trials — after taking Viagra. Other measurements of cardiac function carried out among the trial patients mirrored the findings. The use of Viagra to treat PPH has just been approved by the US Food and Drug Administration (FDA) and Pfizer expects physicians in Oman to start using it for this purpose very soon.
Launched seven years ago, Viagra has been prescribed to more than 23 million men around the world, and use among young men in the Gulf has increased significantly in the past four years.
| 
