Potassium Channel Opener Pinacidil Induces Relaxation of the Isolated Human Radial Artery

Abstract

Abstract. Taking into consideration that the search for drugs capable of modifying blood flow through human radial artery (RA) is warranted, the present study was designed to examine the vasodilatatory effects of the potassium channel opener, pinacidil on the RA and to define the contribution of different K + -channel subtypes in the endothelium-independent pinacidil action on this blood vessel. Pinacidil relaxed the RA rings with endothelium and without endothelium with comparable potency. N-nitro-L-arginine methyl ester (L-NAME) and methylene blue did not affect the pinacidil-induced vasorelaxation in rings with endothelium. In the rings without endothelium, the K + -channel blockers glibenclamide and tetraethylammonium (TEA) moderately antagonized the pinacidil-induced relaxation, while charybdotoxin and 4-aminopiridine did not. In endothelium-denuded rings, precontracted with 100 mM K + , the relaxant responses to pinacidil were highly significantly shifted to the right compared to those obtained in RA precontracted with phenylephrine, but pinacidil-induced maximal relaxation was not affected. Addition of nifedipine did not but addition of nifedipine and nickel (Na + -Ca 2+ exchanger inhibitor) did cause a statistically significant rightward shift of the pinacidil concentration-relaxation curve, although the effect 0.1 mM pinacidil was preserved. Thus, pinacidil induces relaxation of the human RA in endothelium-independent manner, and glibenclamide-and TEA-sensitive vascular smooth muscle K + channels are probably involved. Its ability to completely relax the RA precontracted with K + -rich solution suggests that pinacidil has additional K + channel-independent mechanism(s) of action. It seems that stimulation of the forward mode of the Na + -Ca 2+ exchanger plays a part in this K + channel-independent effect of pinacidil.

Modulation of Noradrenergic Neurotransmission in Isolated Rat Radial Artery

“…K ATP -channel openers attenuate vasoconstriction in response to α 1 -adrenoceptor activation (40) and induce relaxation in human radial arteries (41) or inhibit EFSevoked contraction in human IMA and saphenous vein (42). However, the lack of an effect of glibenclamide observed here suggests that K ATP channels are not involved in adrenergic contractions.…”

Attenuation of receptor-dependent and -independent vasoconstriction in the human radial artery☆

“…Pinacidil, which shares a common binding site with minoxidil sulphate and nicorandil on the K ATP channel, has also demonstrated its ability to reverse phenylephrine-induced contraction in human radial artery [23]. Therefore the activation of K ATP channels would be expected to reverse membrane depolarisation, inhibit calcium influx across the plasma membrane and relax the precontracted radial artery [11].…”

Uloga pola i endotela u relaksantnom efektu pinacidila na izolovanim krvnim sudovima normotenzivnih i spontano hipertenzivnih pacova

“…U proces relaksacije su vjerovatno uključeni K ATP kanali. Međutim, postoje pretpostavke da pinacidil u svom djelovanju uključuje, ne samo otvaranje ove vrste kalijumskih kanala, već i drugih vrsta K + kanala, ali i signalne puteve NO [4]. Jasno je da razvoj spečifičnijeg i efektivnijeg antihipertenzivnog agensa ostaje važan zadatak i vjerujemo dа ćе modulatori funkcije kalijumskih kanala i NO i/ili njihova interakcija tu naći svoje mesto.…”

“…Nasuprot tome, Gollash i saradnici [27] su u studiji na humanoj koronarnoj arteriji dobili da je efekat pinacidila endotel nezavisan. Takođe, Stojnic i saradnici [4] su ispitivali dejstvo pinacidila na humanoj radijalnoj arteriji i njihovi rezultati ukazuju da pinacidil ima endotel nezavisan mehanizam dejstva. Dosadašnja eksperimentalna istraživanja nisu u dovoljnoj mjeri dala odgovor na pitanje učešća endotela i/ili interakcije endotela sa K + kanalima u dilatatornom dejstvu pinacidila na mezenteričnoj i renalnoj arteriji pacova.…”