Tags

Type your tag names separated by a space and hit enter

Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme.
J Cardiovasc Pharmacol. 1995 Aug; 26(2):233-40.JC

Abstract

Antagonists of the type 1 (AT1) angiotensin II (Ang II) receptor increase renin secretion and plasma Ang II levels, and the increased Ang II levels may counteract the effects of the antagonist. Moreover, other investigators have suggested that the reactive increase in Ang II levels may increase bradykinin (BK) levels through stimulation of the type 2 Ang II receptor (AT2). We investigated the acute effects of the AT1 receptor antagonist losartan (intraarterial injection of 10 mg/kg every 12 h) in male Sprague Dawley rats by measuring circulating angiotensin and BK peptides at 6, 12, and 24 h. Whereas acute losartan administration increased blood angiotensin levels four- to sixfold, blood BK levels were unchanged. We also investigated the effects of losartan administered for 8 days (10 mg/kg every 12 hours, by intraperitoneal injection) on circulating and tissue levels of angiotensin and BK peptides, and angiotensin-converting enzyme (ACE). Losartan increased plasma renin levels 100-fold; plasma angiotensinogen levels decreased to 24% of control; and plasma aldosterone levels were unchanged. Ang II levels in plasma, adrenal, lung, heart, and aorta were increased 25-, 8-, 3.5-, 2.4-, and 14-fold, respectively, by losartan administration. By contrast, kidney Ang II levels decreased to 71% of control, accompanied by a decrease in kidney levels of BK-(1-7) and BK-(1-9). No other tissue showed a change in BK peptide levels, except for a reduction in blood levels of BK-(1-8) to 43% of control. Plasma ACE increased by 13-50%, but tissue ACE levels were unchanged. These data demonstrate that losartan has tissue-specific effects on endogenous levels of angiotensin and BK peptides and indicate that increased BK levels do not contribute to the actions of losartan. The absence of a reactive increase in endogenous kidney levels of Ang II indicates that this tissue is likely to be the most sensitive to AT1 receptor antagonism.

Authors+Show Affiliations

St. Vincent's Institute of Medical Research, Fitzroy, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7475048

Citation

Campbell, D J., et al. "Effects of Losartan On Angiotensin and Bradykinin Peptides and Angiotensin-converting Enzyme." Journal of Cardiovascular Pharmacology, vol. 26, no. 2, 1995, pp. 233-40.
Campbell DJ, Kladis A, Valentijn AJ. Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. J Cardiovasc Pharmacol. 1995;26(2):233-40.
Campbell, D. J., Kladis, A., & Valentijn, A. J. (1995). Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. Journal of Cardiovascular Pharmacology, 26(2), 233-40.
Campbell DJ, Kladis A, Valentijn AJ. Effects of Losartan On Angiotensin and Bradykinin Peptides and Angiotensin-converting Enzyme. J Cardiovasc Pharmacol. 1995;26(2):233-40. PubMed PMID: 7475048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. AU - Campbell,D J, AU - Kladis,A, AU - Valentijn,A J, PY - 1995/8/1/pubmed PY - 1995/8/1/medline PY - 1995/8/1/entrez SP - 233 EP - 40 JF - Journal of cardiovascular pharmacology JO - J. Cardiovasc. Pharmacol. VL - 26 IS - 2 N2 - Antagonists of the type 1 (AT1) angiotensin II (Ang II) receptor increase renin secretion and plasma Ang II levels, and the increased Ang II levels may counteract the effects of the antagonist. Moreover, other investigators have suggested that the reactive increase in Ang II levels may increase bradykinin (BK) levels through stimulation of the type 2 Ang II receptor (AT2). We investigated the acute effects of the AT1 receptor antagonist losartan (intraarterial injection of 10 mg/kg every 12 h) in male Sprague Dawley rats by measuring circulating angiotensin and BK peptides at 6, 12, and 24 h. Whereas acute losartan administration increased blood angiotensin levels four- to sixfold, blood BK levels were unchanged. We also investigated the effects of losartan administered for 8 days (10 mg/kg every 12 hours, by intraperitoneal injection) on circulating and tissue levels of angiotensin and BK peptides, and angiotensin-converting enzyme (ACE). Losartan increased plasma renin levels 100-fold; plasma angiotensinogen levels decreased to 24% of control; and plasma aldosterone levels were unchanged. Ang II levels in plasma, adrenal, lung, heart, and aorta were increased 25-, 8-, 3.5-, 2.4-, and 14-fold, respectively, by losartan administration. By contrast, kidney Ang II levels decreased to 71% of control, accompanied by a decrease in kidney levels of BK-(1-7) and BK-(1-9). No other tissue showed a change in BK peptide levels, except for a reduction in blood levels of BK-(1-8) to 43% of control. Plasma ACE increased by 13-50%, but tissue ACE levels were unchanged. These data demonstrate that losartan has tissue-specific effects on endogenous levels of angiotensin and BK peptides and indicate that increased BK levels do not contribute to the actions of losartan. The absence of a reactive increase in endogenous kidney levels of Ang II indicates that this tissue is likely to be the most sensitive to AT1 receptor antagonism. SN - 0160-2446 UR - https://www.unboundmedicine.com/medline/citation/7475048/Effects_of_losartan_on_angiotensin_and_bradykinin_peptides_and_angiotensin_converting_enzyme_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=7475048.ui DB - PRIME DP - Unbound Medicine ER -