Prostaglandin & Vasoconstriction/ Future tx w/ respect to flushing?

July 8, 2000

Medscape

Increased Production of PGHS-2 With Aging Increases Vasoconstriction

WESTPORT, Jul 07 (Reuters Health) - Prostaglandin H synthase-2 (PGHS-2)

increases with age causing increased vasoconstriction in female rats,

according to Canadian researchers.

" We were looking at how aging affected vascular function in the female, "

Dr. T. ge from the University of Alberta, Edmonton, Canada,

told Reuters Health. " Our interest, " she said, " is studying estrogen's

effect on vascular function and to understand more about how vascular

function changes in aging. Our goal is to develop other therapies beside

hormone replacement. "

Dr. ge and colleagues studied mesenteric arteries from 3-month-old

and 12-month-old female Sprague-Dawley rats. They found that there was a

blunting of the relaxation response to methacholine with increasing age,

according to their report in the June issue of Hypertension: Journal of

the American Heart Association.

They also found that the prostaglandin pathway was the predominant

mechanism by which this was occurring. " In this case we found that it

was specifically an isoform of the pathway, the enzyme called PGHS-2.

And, it is this isoform that seemed to be upregulated in aging that

contributed to the vasoconstriction, " Dr. ge explained.

" The reason we think this is exciting, " she said, " is because

pharmaceutical companies are coming up with these 'super aspirins',

which are targeted only to the PGHS-2 enzyme, " which is also known as

COX-2. " But, " Dr. ge explained, " nobody had known that PGHS-2 was

an important player in the cardiovascular system. "

Targeting this enzyme may lead to more specific therapeutic approaches

to improving cardiovascular health. " And this is important for both men

and women because men aren't going to take estrogen, " she added.

" Right now we have a model going where we are inhibiting PGHS-2, in

vivo, in rats, " Dr. ge noted. The team wants to see if it has a

beneficial effect, and if PGHS-2 inhibitors can be used in the

long-term. " This is not directly relevant today to women but I hope it

will be, " Dr. ge added.

Hypertension 2000;35:1242-1247.

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