Angiotensin biosynthesis and concentrations in brain of normotensive and hypertensive rats.
We report here on the extraction and characterization of angiotensin I (ANG I) and angiotensin II (ANG II) from the brain of rats. High pressure liquid chromatography (HPLC) with different mobile phases combined with specific radioimmunoassays (RIA) proved to be a powerful tool for peptide characterization in biological samples; (Ile5)-ANG I, (Ile5)-ANG II and (Ile5)-ANG III could clearly be identified in cerebrospinal fluid (CSF), incubated in vivo and in vitro with renin, in total brain extracts, as well as in hypothalamus (HT), medulla oblongata (MO), cerebellum (CER) and cortex (CO). Angiotensin cleaved from CSF angiotensinogen and angiotensin extracted from brain showed retention times identical to those of plasma angiotensin and synthetic standard peptides, indicating that their amino acid sequence is probably identical. ANG I and ANG II were highest in the HT and lowest in the CO. Following bilateral nephrectomy (NX) both ANG I and ANG II persisted at control levels. Young 10 week old spontaneously hypertensive rats (SHRSP) showed significantly lower ANG I and ANG II concentrations in the HT compared with Wistar Kyoto rats (WKY). Intracerebroventricular (i.c.v.) administration of the converting enzyme inhibitor captopril caused a significant increase in ANG 1 in nephrectomized SHRSP but not in WKY. These differences were not found in 40 week old SHRSP. The data show that ANG I and ANG II are synthetized in the brain of rats. The lower concentrations and the enhanced accumulation of ANG I after converting enzyme blockade in nephrectomized young SHRSP indicate an increased turnover of angiotensin in hypertensive rats.
D000803:Angiotensin I / Q000096:biosynthesis* / Q000302:isolation & purification; D000804:Angiotensin II / Q000096:biosynthesis* / Q000302:isolation & purification; D000805:Angiotensin III / Q000302:isolation & purification; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D010446:Peptide Fragments / Q000302:isolation & purification; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014018:Tissue Distribution
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D010446:Peptide Fragments; D000804:Angiotensin II; D000805:Angiotensin III; D000803:Angiotensin I; D002216:Captopril