selachyl-alcohol and Hypertension--Renovascular

Medullipin I causes a delayed onset depressor response when injected intravenously into rats. The glyceryl compounds selachyl alcohol (SA) and monoolein (MO) cause similar vasodepression. The neutral lipid 1-O-hexadecyl-2-acetyl-sn-glycerol (HAG) was suggested by Blank et al to be medullipin I (Med I, formerly ANRL). Biologic comparisons were made between Med I and various glyceryl compounds, including SA, MO, HAG, alkyl glyceryl ethers of phosphatidyl choline (termed APRL by us), diacylated SA, and the n-butyl boronic acid derivative of SA and MO. The n-butyl boronic acid derivative of Med I also was evaluated. The delay in onset of the depressor response to Med I was reduced by the injection of Med I into the portal vein; that of SA and MO was not. Med I, SA, and MO were activated by the liver, while APRL and HAG were not. Tween 20 inhibited Med I, SA, and MO, but not APRL and HAG. Proadifen (SKF 525A) inhibited Med I, but not SA and MO. The n-butyl boronic acid derivatives of SA, MO, and Med I were inactive. Med I, like SA and MO, appeared to have two hydroxyl groups in close proximity. It was concluded that Med I is neither HAG, APRL, SA, nor MO.

Topics: Animals; Antihypertensive Agents; Fatty Alcohols; Glycerides; Hypertension, Renovascular; Lipids; Male; Platelet Activating Factor; Rats; Rats, Inbred Strains; Vasodilator Agents

Selachyl alcohol (SA) is a mono-oleyl glyceryl ether. It has certain biologic activities similar to those of the antihypertensive neutral renomedullary lipid (ANRL) derived from the renal papilla and its renomedullary interstitial cells (RIC). These include a vaso-depressor effect following bolus injection and a requirement for hepatic activation for the development of biological activity. In view of this similarity to ANRL, it appeared worthwhile to test the antihypertensive action of SA when given via the GI tract. Accordingly, pure SA was given either by gavage or by tube into the stomach or duodenum of one-kidney, one-clip hypertensive rats (5-10 mg per dose). The role of hepatic activation was demonstrated by comparing the BP response to bolus injection of SA and ANRL with and without the presence of an intact circulation to the liver. Administration of SA via the GI tract resulted in a significant decline in BP without tachycardia or weight loss. In the absence of a circulation to the liver, neither SA nor ANRL was active. SA appears to be an effective antihypertensive agent when given via the GI tract.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Fatty Alcohols; Hypertension, Renovascular; Liver Circulation; Male; Rats; Rats, Inbred Strains