Central peptidergic stimulation in blood pressure control: role of enkephalins in rats.

1. The central blood pressure effects of the enkephalin analogue, D-Ala'-Met-enkephalin were investigated in normotensive rats and in spontaneously hypertensive rats. 2. In conscious Wistar rats, injection of 1.7, 17 and 170 nmol of D-Ala'-Met-enkephalin into the lateral brain ventricle produced dosedependent blood pressure increases of 5 + 3 f 1 8, 10.5 f 2.8 and 15.3 f 3.0 mmHg respectively. In contrast, in cr-chloralose-anaesthetized rats, the same doses of the enkephalin analogue produced dose-dependent blood pressure falls of -8.9 f 1.9, -11.1 f 5.2 and -19.8 f 8.4 mmHg. 3. The pressor responses to 170 nmol of D-Ala'-Met-enkephah were blocked by intracerebroventricular pretreatment with the opiate receptor antagonists diprenorphine and naloxone at doses of 10-500 nmol. The depressor effects under anaesthesia were blocked by diprenorphine (10-100 nmol) but not by naloxone. 4. Spontaneously hypertensive rats showed enhanced pressor responses to centrally applied enkephalin when compared with normotensive rats. 5. Central injection of diprenorphine alone produced an initial short blood pressure increase followed by a long-lasting blood pressure fall, which was significantly greater in spontaneously hypertensive iats than in normotensive rats. 6. The results indicate that the central blood pressure effects of enkephalins depend on the state of consciousness and are mediated through naloxoneand diprenorphine-sensitive opioid receptors. 7. The increased sensitivity to centrally applied enkephalins and the depressor responses to the intracerebroventricular injection of diprenor-