Regulatory role of bradykinin in the coronary and cerebral circulations and in systemic hemodynamics.
Bradykinin (BK) increased carotid blood flow (CBF) and jugular nitric oxide (NO) levels when administered into the common carotid artery of rabbits, and potentiated selectively, when infused together with histamine (HIST) or serotonin (5-HT), their effects on both CBF and jugular NO levels (but not vice versa). Such a potentiation was prevented and reversed only by nitroarginine or 1,10-phenanthroline (PHE) (which also reduced basal jugular NO levels) and did not involve the BK1 or BK2 receptors. Either HIST or 5-HT potentiated (likely involving the H1 and 5-HT2 receptors, respectively) the activating effect of BK on kininase I (K1), thus increasing the availability of L-arginine for the synthesis of NO. In patients with migraine, venous NO and K1 activity were higher during HIST desensitization than in basal conditions; moreover, HIST reduced the activities of prekallikrein (pre-KAL), kallikrein (KAL) and kininase II (K2) in the venous blood of these patients, in which the intensity of pain was related to the levels of plasma NO, and the administration into the humeral artery during circulatory arrest of BK alone (but not HIST) or BK and HIST together caused a strong pain attack. BK was confirmed to interact selectively with other autacoids in regulating systemic and local hemodynamics through the system of NO.
Volpe
A R
AR
Receptor Chemistry Centre, Catholic University School of Medicine, Rome, Italy. a.volpe@uniserv.ccr.rm.cnr.it
Fontecchio
G
G
Carmignani
M
M
D000109:Acetylcholine / Q000008:administration & dosage; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D004743:Enkephalin, Leucine / Q000008:administration & dosage; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D011817:Rabbits; D012701:Serotonin / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects
D012701:Serotonin; D004743:Enkephalin, Leucine; D006632:Histamine; D000109:Acetylcholine; D001920:Bradykinin