What is the effect of Losartan (an angiotensin II receptor antagonist) on renin, angiotensin I, angiotensin II, aldosterone, and bradykinin?

From the FDA Drug Label

1. 1 Mechanism of Action Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)] is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system, and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland).
2. 2 Pharmacodynamics Losartan inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 25 to 40% inhibition persisting for 24 hours Removal of the negative feedback of angiotensin II causes a doubling to tripling in plasma renin activity and consequent rise in angiotensin II plasma concentration in hypertensive patients. Losartan does not affect the response to bradykinin, whereas ACE inhibitors increase the response to bradykinin. Aldosterone plasma concentrations fall following losartan administration

The effect of Losartan on various components of the renin-angiotensin system and bradykinin is as follows:

• Renin: Losartan causes a doubling to tripling in plasma renin activity due to the removal of the negative feedback of angiotensin II.
• Angiotensin I: Losartan inhibits the pressor effect of angiotensin I infusions.
• Angiotensin II: Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II and causes a rise in angiotensin II plasma concentration due to the removal of the negative feedback.
• Aldosterone: Losartan causes a fall in aldosterone plasma concentrations.
• Bradykinin: Losartan does not affect the response to bradykinin 1

From the Research

Effects of Losartan on the Renin-Angiotensin-Aldosterone System

• Losartan, an angiotensin II receptor antagonist, inhibits the renin-angiotensin system specifically and selectively without the agonistic effects of peptide receptor antagonists or the bradykinin-potentiating effects of angiotensin converting enzyme (ACE) inhibitors 2.
• Losartan increases plasma renin activity and angiotensin II levels, with the increases being greater at 2 weeks than at 6 weeks of treatment 3.
• The drug decreases plasma aldosterone concentration, with the effect being dose-related 3.
• Losartan blocks the aldosterone and renal vascular responses to angiotensin II in humans, with the effect being more pronounced under low salt conditions 4.

Effects of Losartan on Bradykinin

• Losartan binds and activates bradykinin B2 receptor signaling, working as a partial agonist compared to the endogenous ligand bradykinin 5.
• The activation of bradykinin B2 receptor signaling by losartan may contribute to its cardioprotective effects 5.
• However, another study found that losartan does not increase bradykinin levels, and that the absence of a reactive increase in endogenous kidney levels of angiotensin II indicates that this tissue is likely to be the most sensitive to AT1 receptor antagonism 6.

Summary of Effects

• Losartan increases renin and angiotensin II levels, while decreasing aldosterone levels.
• The drug has a blocking effect on the aldosterone and renal vascular responses to angiotensin II.
• Losartan activates bradykinin B2 receptor signaling, but its effect on bradykinin levels is unclear, with different studies reporting different results 3, 4, 5, 6.