Kinins and Kinin Receptors in Cardiovascular and Renal Diseases

Abstract

This review addresses the physiological role of the kallikrein-kinin system in arteries, heart and kidney and the consequences of kallikrein and kinin actions in diseases affecting these organs, especially ischemic and diabetic diseases. Emphasis is put on pharmacological and genetic studies targeting kallikrein; ACE/kininase II; and the two kinin receptors, B1 (B1R) and B2 (B2R), distinguished through the work of Domenico Regoli and his collaborators. Potential therapeutic interest and limitations of the pharmacological manipulation of B1R or B2R activity in cardiovascular and renal diseases are discussed. This discussion addresses either the activation or inhibition of these receptors, based on recent clinical and experimental studies.

Keywords: angiotensin-converting enzyme/kininaseII; arteries; diabetes; heart; ischemic heart disease; kallikrein; kidney; kinin receptors; kinins.

Figure 1

Alternate use of B2R and B1R in cardioprotection in non-diabetic and diabetic mice, respectively, during cardiac ischemia-reperfusion. B1R ago: pharmacological B1R agonist; B2R ago: pharmacological B2R agonist. G: G proteins; pAkT: phosphoinositide 3 kinase/Akt; pERK1/2: extracellular signal-regulated kinase1/2; pGSK3b: glycogen synthase-kinase3; p is for phosphorylated forms of the enzymes. Note that B1R but not B2R synthesis increases more than three times in the diabetic heart. Infarct size-reducing effect is associated with activation of the so-called “Reperfusion Ischemia Salvage Kinase (RISK)” pathway and inhibition of GSK-3β. Based on data presented in [71].