Which of the following statements is correct about bradykinin? (DNB June 2012)
|A||Captopril inhibits its metabolic inactivation|
|B||Drugs that are metabolized to, or generate, nitric oxide, counteract bradykinin’s vascular effects|
|C||Increased blood pressure is the predominant cardiovascular response|
|D||Newer H1 blockers (e.g., fexofenadine; “second-generation” antihistance) also competitively block bradykinin receptors|
a. Bradykinin is metabolized to biologically inactive peptides by an enzyme that has three names: angiotensin converting enzyme, bradykininase, and kininase II.
b. Bradykinin, whether injected experimentally or derived from endogenous sources (kininogens cleaved by specific proteases called kallikreins), exerts significant vasodilator effects that can lower systolic and diastolic blood pressures.
c. Although this may not be an important pressure-regulating mechanism in normotensive individuals, it probably is in many (most?) patients with essential hypertension.
d. Recall that ACE inhibitors lower blood pressure in many hypertensive patients. One mechanism involves "preserving" bradykinin by inhibiting its enzymatic inactivation. Bradykinin also causes prerenal arteriolar vasodilation and increases GFR, leading to diuretic effects.
e. The peptide's vascular effects are mediated by endothelial cell-derived nitric oxide, and they are enhanced by other drugs that cause vasodilation by a nitric oxide-related mechanism.
f. Bradykinin receptor blockers prevent the peptide's vasodilator effects. Icatibant is a 10 aminoacid peptide that is bradykinin receptor blocker.
g. The drug is considered to be an orphan drug in many countries. Presently, the drug has been approved only for one indication i.e. hereditary angioneuretic angioedema,