Analogs of Phosphatidylcholine: α-Adrenergic Antagonists from the Renal Medulla

SUMMARY Antihypertensive polar renomedallary lipid (APRL), a conglomerate of l-0-alkyl-2-acetoylgtycero-3-pfaospbocboliiie analogs, was tested in 4- to 6-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats using mlcrodrculatory techniques. APRL (0.5 μg/ml), when added to the solution bathing the cremaster musde, caused significant changes in the diameter, red blood cell velocity, and blood flow In both groups of rats, for arterioles and venules. Arteriolar changes in diameter were significantly greater (p < 0.05) in SHR than in WKY. Mlcropipette application of APRL indicated a dosedependent response for arterioles and venules in both groups. Moreover, the potent nature of this compound was demonstrated. Relative potency of APRL given intravenously was tested in 10- to 12-weck-old SHR and WKY. Tbe response curve was shifted significantly to the left for SHR (p < 0.01). APRL interaction with known controllers of blood flow was tested in SHR. Blockade of cnolinergic, β-adrenergic, or histaminergic receptors did not inhibit APRL action. Blockade of prostaglandin or bradykinin synthesis did not prevent depression of blood pressure by APRL. APRL (40 μg/kg) inhibited (p < 0.001) the pressor response to norepinephrine (1-10 μg/kg) but not to angiotensin II (4 μg/kg)- The present study provides direct evidence that APRL is a vasodilator with increased potency in SHR hypertension. The acute vascular response may be mediated by alpha-adrenergic antagonism.