angiotensin-iii and Hypertension--Renal

Antihypertensive effects of an angiotensin (Ang) II receptor antagonist, candesartan cilexetil (TCV-116), were compared with those of an angiotensin converting enzyme (ACE) inhibitor, enalapril, in spontaneously hypertensive rats (SHR), 2-kidney, 1-clip hypertensive rats (2K, 1C-HR) and 1-kidney, 1-clip hypertensive rats (1K, 1C-HR). CV-11974, the active form of TCV-116, had no inhibitory activity for plasma ACE. In rats, TCV-116 inhibited the pressor responses to Ang I, Ang II, and Ang III without an effect on the bradykinin (BK)-induced depressor response. Enalapril inhibited only the Ang I-response and potentiated the BK-response. In SHR, the antihypertensive effect of TCV-116 (10 mg/kg) was larger than the maximum antihypertensive effect of enalapril and was not intensified by combination with enalapril. Administration of CV-11974 potentiated the maximum antihypertensive effect of enalapril. Although both agents reduced blood pressure in 2K, 1C-HR, only TCV-116 had a marked antihypertensive effect in 1K, 1C-HR. These findings indicate that TCV-116 is more effective than enalapril in reducing blood pressure in SHR and 1K, 1C-HR, and that the BK- and/or prostaglandin-potentiating effect of enalapril contributes little to its antihypertensive mechanism in SHR.

Topics: Administration, Oral; Angiotensin I; Angiotensin II; Angiotensin III; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Bradykinin; Enalapril; Enzyme Activation; Hypertension, Renal; Male; Peptidyl-Dipeptidase A; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renal Artery; Surgical Instruments; Tetrazoles; Vasoconstrictor Agents

1 Prolonged infusion (11 h) of both saralasin and angiotensin-converting enzyme inhibitor (SQ20881) gradually lowered BP in two-kidney hypertensive rats to levels similar to that in normotensive rats infused with dextrose. 2 Saralasin did not lower BP in DOCA-salt hypertensive rats. 3 These observations support the notion that in chronic renal hypertension, angiotensin II may maintain hypertension by a slowly developing action. 4 Plasma angiotensin II in rats infused with SQ20881 was suppressed relative to renin, but was not eliminated. 5 Chromatography of angiotensin II extracts from dogs infused with converting enzyme inhibitor (SQ14,225) showed that the very high levels of angiotensin I achieved after treatment with SQ14,225 can lead to falsely high estimated angiotensin II levels as a result of angiotensin I cross-reacting with the angiotensin II assay.

Topics: Angiotensin I; Angiotensin II; Angiotensin III; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Disease Models, Animal; Dogs; Female; Hypertension, Renal; Male; Oligopeptides; Proline; Rats; Saralasin; Teprotide

Topics: Adrenal Gland Diseases; Adult; Angiotensin II; Angiotensin III; Humans; Hypertension; Hypertension, Renal; Male

Topics: Adolescent; Adult; Angiotensin II; Angiotensin III; Blood Pressure; Child; Female; Humans; Hypertension, Renal; Male; Prostaglandins A; Vascular Resistance