Mechanisms underlying the biphasic effect of vitamin K1 (phylloquinone) on arterial blood pressure.
Phylloquinone (vitamin K(1), VK(1)) is widely used therapeutically and intravenous administration of this quinone can induce hypotension. We aimed to investigate the mechanisms underlying the effects induced by VK(1) on arterial blood pressure. With this purpose a catheter was inserted into the abdominal aorta of male Wistar rats for blood pressure and heart rate recording. Bolus intravenous injection of VK(1) (0.5-20 mgkg(-1)) produced a transient increase in blood pressure followed by a fall. Both the pressor and depressor response induced by VK(1) were dose-dependent. On the other hand, intravenous injection of VK(1) did not alter heart rate. The nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10 and 20 mgkg(-1)) reduced both the increase and decrease in blood pressure induced by VK(1) (5 mgkg(-1)). On the other hand, indometacin (10 mg kg(-1)), a non-selective cyclooxygenase inhibitor, did not alter the increase in mean arterial pressure (MAP) induced by VK(1). However, VK(1)-induced fall in MAP was significantly attenuated by indometacin. We concluded that VK(1) induces a dose-dependent effect on blood pressure that consists of an acute increase followed by a more sustained decrease in MAP. The hypotension induced by VK(1) involves the activation of the nitric oxide (NO) pathway and the release of vasodilator prostanoid(s).
Tirapelli
Carlos R
CR
Department of Psychiatry Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil. crtirapelli@eerp.usp.br
Resstel
Leonardo B M
LB
de Oliveira
Ana M
AM
Corrêa
Fernando M A
FM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D010837:Vitamin K 1 / Q000494:pharmacology*
D009569:Nitric Oxide; D010837:Vitamin K 1; D019331:NG-Nitroarginine Methyl Ester