Brain Angiotensin-converting Enzyme Activity Research Articles

The effect of morphine, naloxone, D- and L-aspartic acid on the brain and lung ACE in mice

The brain and lung angiotensin converting enzyme (ACE) activities of the mice injected with 10 mg/kg morphine and/or naloxone, 200 mg/kg D- and/or L-aspartic acid were spectrophotometrically determined. Morphine, naloxone, D- and L-aspartic acid alone inhibited both brain and lung ACE activities whereas the combinations of morphine with naloxone, D-aspartic acid with L-aspartic acid and morphine with naloxone + L-aspartic acid showed no inhibitory effect on the brain ACE. While naloxone or L-aspartic acid partly antagonized the suppression of morphine on the lung ACE their combination completely prevented morphine from inhibiting the lung ACE. In the in vivo experiments performed on the brain and lung homogenates of the untreated mice the determination of the ACE activity in the incubating media containing 3.10(-3) M morphine or naloxone, 10(-2) M D- or L-aspartic acid showed a significant decrease in the activity. But no in vitro antagonistic effect was found by using the combinations of the drugs used in the study. The antagonism seen in the in vivo experiments was considered as an indirect one. And the relationship between the inhibitory effect of morphine, naloxone and D-aspartic acid, their suppressive effect on drinking and their beneficial effects in various forms of shock was discussed.

Attenuation of pressor responses to intracerebroventricular angiotensin I by angiotensin converting enzyme inhibitors and their effects on systemic blood pressure in conscious rats

The components of the renin-angiotensin system exist in the brain but their physiological role is uncertain. The effects of two angiotensin converting enzyme (ACE) inhibitors, MK 421 (or its diacid) and captopril, on brain ACE activity, as measured by inhibition of the pressor response to intracerebroventricularly (i.c.v.) administered angiotensin I (AI), and the potential contribution of the central nervous system to their antihypertensive activity were evaluated in the present series of experiments. The diacid of MK 421 (1 and 10 ug) and captopril (3 and 10 ug) given i.c.v. to conscious normotensive rats reduced the pressor response to i.c.v. AI indicating that they can inhibit brain ACE. Responses to AII were unaffected. Oral administration of maximal antihypertensive doses of MK 421 (10 mg/kg) and of captopril (30 mg/kg) to normotensive rats did not attenuate pressor responses to i.c.v. AI indicating that brain ACE was not inhibited under these circumstances. Intracerebroventricular administration of MK 421 diacid, (10 and 30 ug) and captopril (30 and 100 ug) did not lower baseline blood pressure of spontaneously hypertensive rats. These experiments indicate that MK 421 and captopril can inhibit brain ACE but that the central renin-angiotensin system probably does not contribute to their antihypertensive activity.

Brain angiotensin-converting enzyme activity in experimental hypertension in the rats

Brain angiotensin-converting enzyme activity in experimental hypertension in the rats

Modulation of brain angiotensin-converting enzyme by dietary sodium and chronic intravenous and intracerebroventricular fusion of angiotensin II.

Angiotensin-converting enzyme (ACE) in rat brain closely resembled that in lung in its kinetics with the substrate Hip-His Leu, the inhibitors SQ 20,881 and SQ 14,225, and iun its Cl- activation profile. Modification of dietary NaCl intake was associated with marked changes in brain ACE activity. Sodium-loaded rats had lower activity of ACE in hypothalamus, striatum, and midbrain, and higher activity in spinal cord compared to controls. In sodium-restricted rats, ACE was elevated in pituitary and depressed in spinal cord. Chronic intravenous infusion of angiotensin (AII) was associated with a pattern of changes partly resembling sodium loading: ACE was depressed in hypothalamus and striatum but elevated in midbrain. After chronic intracerebroventricular infusion of AII, ACE was elevated in striatum and hippocampus, and depressed in spinal cord; a pattern of changes quite different from those associated with intravenous AII. These results show that ACE in several brain regions is sensitive to dietary sodium intake and support the hypothesis that angiotensin-containing neurons in these areas might be responsive to NaCl status of the animal. The observed changes in brain ACE do not seem to be explained in any simple manner by changes in circulating or central angiotensin II.

Brain angiotensin-converting enzyme activity in experimental hypertensive rats.

Angiotensin-converting enzyme (ACE) activity was measured in six areas of the brain of normotensive and experimental hypertensive rats; one-clip, one-kidney (1-c, 1-k) and one-clip, two-kidney (1-c, 2-k) Goldblatt hypertensive (GH) rats. ACE activity was consistently high in the thalamus of normotensive and both 1-c, 1-k and 1-c, 2-k GH rats. However, the enzyme activity in the hypothalamus of 1-c, 2-k GH rats was significantly higher than that of normotensive rats, while there was no significant difference in the enzyme activity between normotensive and 1-c, 1-k GH rats. These results demonstrate that in 1-c, 2-k GH rats, increased ACE activity in the brain may play a central role in the hypertension.

Effect of sodium intake on brain angiotensin-converting enzyme activity in spontaneously hypertensive rat.

The effect of sodium intake on angiotensin-converting enzyme activity in five areas of the brain (the cerebral cortex, midbrain, striatum, thalamus and hypothalamus) was studied in normotensive, spontaneously hypertensive and stroke-prone spontaneously hypertensive rats. The enzyme activity was significantly higher in the hypothalamus than in other areas of the brain of spontaneously hypertensive rats. Sodium intake resulted in a significant rise of the enzyme activity in the midbrain of spontaneously hypertensive rats and also in the midbrain and the striatum of stroke-prone spontaneously hypertensive rats. In normotensive rats, however, there was no significant difference in the enzyme activity in any area of brain between the control and the salt-treated group. It is likely therefore that a high circulating sodium level increases angiotensin-converting enzyme content of the brain in spontaneously hypertensive rats, and it is suggested that the increased converting-enzyme activity may play a role in development of hypertension induced by sodium loading.