Mechanisms of kinin B1-receptor-induced hypotension in the anesthetized dog. 1996

D Lamontagne, and N Nakhostine, and R Couture, and R Nadeau
Centre de recherche, Hôpital du Sacré-Coeur de Montréal, Québec, Canada.

Our study was performed to investigate the mechanism underlying the phypotensive effect of kinin B1-receptor activation with des-Arg9-bradykinin (des-Arg9-BK), in comparison with B2-receptor activation with bradykinin (BK), in anesthetized dogs. Bolus intravenous and intraarterial injections of both kinins were compared. BK (0.6 microgram/kg) produced a transient hypotension of the same magnitude, regardless of the route of administration (from 110 +/- 6 mm Hg to 66 +/- 6 mm Hg, or -41 +/- 5%). In contrast, intraarterial injection of des-Arg9-BK (0.6 microgram/kg) induced a weaker hypotension compared with its intravenous injection (-27 +/- 2% vs. -39 +/- 3%, p < 0.05). The hypotension induced by both kinins was accompanied by increases in heart rate, maximum left ventricular dP/dt, and aortic blood flow, suggesting a reduction in peripheral resistance. The positive inotropic and chronotropic effects of BK and des-Arg9-BK were found to be mediated by the sympathetic nervous system, because they were abolished by propranolol. The hypotension induced by intravenous and intraarterial injections of BK and intravenous injections of des-Arg9-BK was only slightly reduced after nitric oxide (NO) synthase inhibition with NG-nitro-L-arginine (L-NNA). In contrast, the hypotensive effect of intraarterial injection of des-Arg9-BK was reduced by half after treatment with L-NNA (p < 0.05). Neither bilateral vagotomy nor ganglionic blockade with pentolinium reduced the hypotension induced by both kinins. In conclusion, the hypotensive effect of des-Arg9-BK and BK results from a peripheral vasodilation. The contribution of NO in this vasodilation is substantial for des-Arg9-BK when administered intraarterial but limited for BK and intravenous des-Arg9-BK.

UI MeSH Term Description Entries
D007022 Hypotension Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients. Blood Pressure, Low,Hypotension, Vascular,Low Blood Pressure,Vascular Hypotension
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D001920 Bradykinin A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg,Bradykinin Acetate, (9-D-Arg)-Isomer,Bradykinin Diacetate,Bradykinin Hydrochloride,Bradykinin Triacetate,Bradykinin, (1-D-Arg)-Isomer,Bradykinin, (2-D-Pro)-Isomer,Bradykinin, (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (2-D-Pro-7-D-Pro)-Isomer,Bradykinin, (3-D-Pro)-Isomer,Bradykinin, (3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (5-D-Phe)-Isomer,Bradykinin, (5-D-Phe-8-D-Phe)-Isomer,Bradykinin, (6-D-Ser)-Isomer,Bradykinin, (7-D-Pro)-Isomer,Bradykinin, (8-D-Phe)-Isomer,Bradykinin, (9-D-Arg)-Isomer,Arg Pro Pro Gly Phe Ser Pro Phe Arg
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260 Female Females
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014628 Vagotomy The interruption or removal of any part of the vagus (10th cranial) nerve. Vagotomy may be performed for research or for therapeutic purposes. Vagotomies

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