Renin-like activity in the rat brain during the development of DOC-salt hypertension.

Abstract

SUMMARY Lerels and distribution of an angiotenslD-fonning enzyme, active at the physiological pH (isorenin), were determined in the central nervous system of 24 rats treated with 25 mg/kg of deoxycorticosterone (DOC) subcutaneously, twice a week, plus saline to drink during 30 days, and in 14 control animals. Different areas of the brain were excised and homogenized. Renin activity and concentration were determined by incubation of the supernatant of each homogenate at pH 7.2 alone and in the presence of an excess of renin substrate. The angiotensin generated was measured by radioimmunoassay. Concentration of the renin-like enzyme was significantly higher in the posterior hypophysis and in the brain stem of the experimental group; isorenin activity was higher in the hypothalamus, cerebral cortex, cerebellum, and brain stem of the DOC-salttreated rats than in the control rats. Changes in the angiotensin-forming enzyme in the central nervous system of experimental animals, active at physiological pH, suggest that this isoreoin system may play a role in the physiological response to DOC-salt in the rat. The significance of the brain isorenin system in the regulation of blood pressure requires further analysis.

Blockade of Angiotensin Receptors in the Anterior Hypothalamic Preoptic Area Lowers Blood Pressure in DOCA-Salt Hypertensive Rats.

“…Furthermore, Wilson et al (27) have demonstrated that the number of angiotensin II binding sites is increased following treatment with mineralocorticoids, even in neuronal cell preparations from brain tissues. In addition, it has been reported that DOCA-salt hypertensive rats show elevated central renin activity (28). In the present study, the pressor response to angiotensin II injection into the AHA was enhanced in DOCAsalt hypertensive rats as compared with that in shamoperated rats.…”

Effects of Centrally Administered Losartan on Deoxycorticosterone-salt Hypertension Rats

“…After DOCA-salt treatment for 1 month, renin-like activity and Ang II in hypothalamus and brain stem nuclei were elevated, but plasma renin activity was very low (7,8). In rats with DOCA-salt hypertension for 4-8 weeks, angiotensin II receptor binding on autoradiography was also elevated in selected brain areas involved in cardiovascular regulation, such as nucleus of solitary tract, area postrema, median preoptic nucleus, subfornical organ, and solitary vagal area (4)(5)(6).…”

“…DOCA-salt-treated rats show higher Ang II receptor density in brain areas involved in cardiovascular regulation, such as the nucleus of solitary tract, area postrema, median preoptic nucleus, subfornical organ, and solitary vagal area (4)(5)(6), and have elevated levels of renin and Ang II in hypothalamus and brain stem nuclei (7,8). Acute intracerebroventricular (icv) administration of captopril decreases the blood pressure of DOCA-salt hypertensive rats (9).…”

Angiotensin II receptors in the solitary-vagal area of hypertensive rats.

“…14 ' 15 There is also evidence that brain Ang II may be involved in the deoxycorticosterone acetate (DOCA)-salt model of hypertension. Although plasma renin activity is depressed in DOCA-salt hypertensive rats, 16 DOCA-salt rats have elevated brain renin activity 17 and increased responsiveness to intracerebroventricular Ang II. 18 The increased responsiveness to intracerebroventricular Ang II is consistent with the demonstration that binding of 12S I-[Sar']Ang II is also elevated in the brains of DOCA-salt rats.…”