A drug that improves function of retinal blood vessels may be able to reduce the risk of stroke

Apr 9 2004

The small study found that endothelial function is abnormal in eye blood vessels of patients who have early-stage hypertension, but that treatment with an angiotensin-receptor blocker (ARB) drug improves endothelial function.  The endothelium is the lining of vessel walls and plays a key role in the vessels’ ability to relax and to constrict. 

Because of the similarity between retinal and brain blood vessels, the findings also suggest that the drug can improve the function of brain vessels, said lead author Christian Delles, M.D., currently a research fellow at the British Heart Foundation Glasgow Cardiovascular Research Center in Glasgow, U.K.

Delles conducted the study at the Clinical Research Center headed by Professor Roland Schmieder at University of Erlangen-Nurnberg in Erlangen, Germany.

 “Studying the reaction of blood vessels in the eyes may offer insight into stroke prevention by revealing how blood vessels in the brain react to high blood pressure, a major risk factor for stroke,” he said.

The study involved 38 young adults (average age 27), half of whom had early-stage hypertension.  The patients randomly received the drug candesartan cilexetil or placebo for seven days, followed by measurements of blood flow in retinal vessels.  Each patient was then switched to the opposite treatment (candesartan or placebo) and treated for another seven days, after which the retinal blood flow studies were repeated.

Two types of retinal blood vessel tests were conducted after each treatment period.  One test involved measurement of blood flow in the central retinal artery before and after light stimulation.  The second type of evaluation assessed blood flow through tiny retinal capillaries before and after administration of L-NMMA, a substance that inhibits production of nitric oxide, a key factor in blood vessels’ ability to expand normally.

In the 19 patients with normal blood pressure, administration of L-NMMA significantly decreased retinal capillary blood flow, and light stimulation significantly increased blood flow velocity in the central retinal artery, results indicating normal blood vessel function.  In contrast, neither test changed blood flow patterns in the retinal vessels of the hypertensive patients during placebo treatment.  However, treatment with candesartan restored the normal pattern of blood vessel activity in patients with high blood pressure.

 In addition to the direct effects of high blood pressure, other factors related to hypertension might contribute to stroke risk, researchers said.  In particular, a signaling network known as the renin-angiotensin-aldosterone system (RAAS) can adversely affect the endothelium.  Drugs that interfere with RAAS, which include angiotensin receptor blockers such as candesartan and angiotensin-converting enzyme (ACE) inhibitors, help restore and maintain normal endothelial function.