Premium
Different Potassium Channels are Involved in Relaxation of Rat Renal Artery Induced by P 1075
Author(s) -
Novakovic Aleksandra,
Pavlovic Marija,
Milojevic Predrag,
Stojanovic Ivan,
Nenezic Dragoslav,
Jovic Miomir,
Ugresic Nenad,
Kanjuh Vladimir,
Yang Qin,
He GuoWei
Publication year - 2012
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2011.00855.x
Subject(s) - potassium , potassium channel , renal artery , chemistry , medicine , relaxation (psychology) , potassium channel blocker , pharmacology , biophysics , cardiology , endocrinology , kidney , biology , organic chemistry
The ATP ‐sensitive K + channels opener ( K ATP CO ), P 1075 [ N ‐cyano‐ N ′‐(1,1‐dimethylpropyl)‐ N ″‐3‐pyridylguanidine], has been shown to cause relaxation of various isolated animal and human blood vessels by opening of vascular smooth muscle ATP ‐sensitive K + ( K ATP ) channels. In addition to the well‐known effect on the opening of K ATP channels, it has been reported that vasorelaxation induced by some of the K ATP CO s includes some other K + channel subtypes. Given that there is still no information on other types of K + channels possibly involved in the mechanism of relaxation induced by P 1075, this study was designed to examine the effects of P 1075 on the rat renal artery with endothelium and with denuded endothelium and to define the contribution of different K + channel subtypes in the P 1075 action on this blood vessel. Our results show that P 1075 induced a concentration‐dependent relaxation of rat renal artery rings pre‐contracted by phenylephrine. Glibenclamide, a selective K ATP channels inhibitor, partly antagonized the relaxation of rat renal artery induced by P 1075. Tetraethylammonium ( TEA ), a non‐selective inhibitor of Ca 2+ ‐activated K + channels, as well as iberiotoxin, a most selective blocker of large‐conductance Ca 2+ ‐activated K + ( BK Ca ) channels, did not abolish the effect of P 1075 on rat renal artery. In contrast, a non‐selective blocker of voltage‐gated K + ( K V ) channels, 4‐aminopyridine (4‐ AP ), as well as margatoxin, a potent inhibitor of K V 1.3 channels, caused partial inhibition of the P 1075‐induced relaxation of rat renal artery. In addition, in this study, P 1075 relaxed contractions induced by 20 mM K + , but had no effect on contractions induced by 80 mM K + . Our results showed that P 1075 induced strong endothelium‐independent relaxation of rat renal artery. It seems that K ATP, 4‐ AP ‐ and margatoxin‐sensitive K + channels located in vascular smooth muscle mediated the relaxation of rat renal artery induced by P 1075.