An orally active inhibitor of the enzyme that converts angiotensin I to angiotensin II (All) and degrades bradykinin has recently been shown to lower blood pressure in spontaneously hypertensive (SH) rats when administered orally, but to have no depressor effect on normotensive Wistar-Kyoto (WKY) rats 7, 1. Since Captopril is a small molecule (2-D-methyl-3-mercapto-propranoyl-L-proline) it might be able to cross the blood-brain barrier and exert its hypotensive action in the brain. On the other hand, it could act peripherally. If it crosses the blood-brain barrier the action might be due to the inhibition of angiotensin II formation since it has been shown that saralasin, an angiotensin II antagonist, lowers blood pressure in SH rats when injected into the brainS, 11.

Therefore, to determine if Captopril has a central action we have compared administration of the same dose intracerebroventricularly (ivt) and intravenously (iv) to SH rats. We reasoned that if the same dose of Captopril produces a greater hypotensive response ivt, than iv it must be acting centrally and not merely leaking into the blood. This was found to be the case. Six male SH rats, 4--5 months of age, weighing 300-350 g, were anesthetized with 20~ chloral hydrate (2 ml/kg). Stainless-steel cannulae were implanted into the left lateral ventricles and heparinized saline-filled catheters were introduced into the left femoral arteries and veins. The venous catheter was polyethelene tubing (PE 50). The arterial catheters were Silastic inside the artery. The Silastic part of the catheter was attached to polyethylene tubing (PE 50) outside the artery. Both catheters were exteriorized by placing them subcutaneously to a cut in the skirt over the back of the rat approximately at the level of the scapulae. The catheters were held in place on the back by wound clips and cranioplastic dental cement. The rats were allowed to recover for at least one day after the operation.