Reduction in renal blood flow following administration of norepinephrine and phenylephrine in septic rats treated with Kir6.1 ATP-sensitive and KCa1.1 calcium-activated K+ channel blockers.
We evaluated the effects of K+ channel blockers in the vascular reactivity of in vitro perfused kidneys, as well as on the influence of vasoactive agents in the renal blood flow of rats subjected to the cecal ligation and puncture (CLP) model of sepsis. Both norepinephrine and phenylephrine had the ability to increase the vascular perfusion pressure reduced in kidneys of rats subjected to CLP at 18 h and 36 h before the experiments. The non-selective K+ channel blocker tetraethylammonium, but not the Kir6.1 blocker glibenclamide, normalized the effects of phenylephrine in kidneys from the CLP 18 h group. Systemic administration of tetraethylammonium, glibenclamide, or the KCa1.1 blocker iberiotoxin, did not change the renal blood flow in control or septic rats. Norepinephrine or phenylephrine also had no influence on the renal blood flow of septic animals, but its injection in rats from the CLP 18 h group previously treated with either glibenclamide or iberiotoxin resulted in an exacerbated reduction in the renal blood flow. These results suggest an abnormal functionality of K+ channels in the renal vascular bed in sepsis, and that the blockage of different subtypes of K+ channels may be deleterious for blood perfusion in kidneys, mainly when associated with vasoactive drugs.
Department of Pharmacology, Universidade Federal do Paraná, Curitiba, PR, Brazil.
Bruna
B
da Rosa Maggi Sant'Helena
Laboratory of Cardiovascular Pharmacology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Karla L
KL
Guarido
Department of Pharmacology, Universidade Federal do Paraná, Curitiba, PR, Brazil.
Priscila
P
de Souza
Laboratory of Cardiovascular Pharmacology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Sandra
S
Crestani
Laboratory of Cardiovascular Pharmacology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: j.e.silva.santos@ufsc.br.
J Eduardo
JE
da Silva-Santos
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology
D054086:KATP Channels; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D026902:Potassium Channel Blockers; C092520:uK-ATP-1 potassium channel; D010656:Phenylephrine; D009638:Norepinephrine
(S)-(+)-Norepinephrine l-bitartrate (PubChem CID: 168929); Calcium chloride (PubChem CID: 6093260); Dimethyl sulfoxide (PubChem CID: 679); Glibenclamide; Glibenclamide (PubChem CID: 3488); Iberiotoxin (PubChem CID: 16132435); Iberiotoxin.; Kidneys; Magnesium sulfate (PubChem CID: 24083); Minoxidil sulfate (PubChem CID: 4202); NS 1619 (PubChem CID: 4552); Phenylephrine hydrochloride (PubChem CID: 5284443); Potassium chloride (PubChem CID: 4873); Potassium dihydrogen phosphate (PubChem CID: 516951); Septic shock; Sodium bicarbonate (PubChem CID: 516892); Sodium chloride (PubChem CID: 5234); Sodium phosphate (PubChem CID: 24203); Tetraethylammonium; Tetraethylammonium chloride (PubChem CID: 5946); d-glucose (PubChem CID: 5793)