Depressor and pressor actions of purine nucleosides and nucleotides in the anaesthetized rat.
In pentobarbitone-chloralose anaesthetized rats, the effects of aortic administration of various purine compounds on systemic arterial pressure were investigated. All animals were pretreated with atropine and guanethidine to (largely) eliminate reflex neurogenic cardiovascular adjustments, and drugs influencing purine receptors, prostaglandin synthesis, etc. were used for analytical purposes. The compounds used were adenosine (AD) and its slowly degradable analogue, 2-chloroadenosine (2-chloro), adenosine-5'-triphosphate (ATP) and its slowly degradable analogues beta, gamma-methyleneATP (beta,gamma-meATP) and alpha,beta-methyleneATP (alpha,beta-meATP). Control cardiac output measurements before, at and after the peak pressure changes in some experiments revealed that they were at least 80% due to changes in systemic resistance, i.e. dominated by shifts in resistance vascular tone. Adenosine, 2-chloro, ATP and beta,gamma-meATP all elicited depressor (vasodilator) responses. 2-chloro was more potent than AD. Furthermore, the results suggest that the depressor action of ATP involves P1-purinoceptors, following the rapid degradation of ATP to AD, and probably also other mechanisms. The stable ATP analogues caused prompt pressor (vasoconstrictor) responses, where alpha,beta-meATP was more potent than beta,gamma-meATP. The latter compound also produced delayed (probably P1-purinoceptormediated) depressor actions, presumably via slow degradation to AD.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D007269:Injections, Intra-Arterial; D008297:Male; D009711:Nucleotides / Q000494:pharmacology*; D011684:Purine Nucleosides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009711:Nucleotides; D011684:Purine Nucleosides; D015762:2-Chloroadenosine; D000255:Adenosine Triphosphate; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate