Inhibition of Coronary Vasodilating Action of Dipyridamole and Adenosine by Aminophylline in the Dog

Abstract

Experiments were performed to determine (1) whether intravenously administered aminophylline inhibits the coronary vasodilating effects of intravenous or intracoronary administration of dipyridamole or adenosine and (2) whether aminophylline locally administered in the coronary artery inhibits the vasodilating action of adenosine given intravenously or injected into the coronary artery. Coronary vasodilator responses to dipyridamole or adenosine were determined before and after administration of aminophylline. Intravenous aminophylline was found to inhibit coronary vasodilatation induced by intravenous or intracoronary dipyridamole or adenosine. After intravenous aminophylline, adenosine administered intravenously or into the coronary artery was 2.5 to 4 times less effective in inducing coronary vasodilatation. Aminophylline injected locally into the coronary artery was also effective in inhibiting coronary vasodilatation induced by intravenous and intracoronary adenosine. The mechanism of this inhibitory phenomenon has not been elucidated. ADDITIONAL KEY WORDSthermodilution flowmeter nitroglycerin acetylcholine coronary sinus blood flow• During our studies to evaluate the coronary vasodilating effects of various agents, we observed that normally effective intravenous doses of dipyridamole, 1 a coronary vasodilator, were not effective in increasing coronary sinus blood flow in dogs previously given aminophylline. In the present paper we report the results of experiments performed to demonstrate inhibition of the coronary vasodilating action of dipyridamole or adenosine by aminophylline. Previous studies had shown that dipyridamole enhances coronary vasodilatation induced by intravenously administered adenosine (1, 2). It was further found that dipyridamole decreases the permeability of the red blood cell membrane to adenosine (3, 4), thus preventing entry of adenosine into the red blood cell where it would be inactivated by the intracellular adenosine deaminase. On the basis of these findings, dipyridamole-induced vasodilatation could be related to an adenosine action. It was for this reason that the present studies were extended to adenosine also.The role of catecholamines, if any, in the inhibition of adenosine-induced coronary vasodilatation by aminophylline was also investigated after beta-receptor blockade. MethodsTwenty-six healthy mongrel dogs were used; all were anesthetized with morphine sulfate, 3 mg/kg subcutaneously, followed in 1 hour by intravenous administration of allobarbital, 12.5 mg/kg, urethane, 50 mg/kg; monoethylurea, 50 mg/kg; and sodium pentobarbital, 8 mg/kg. Femoral arterial blood pressure was recorded on a direct-writing Sanborn Polyviso, from a Statham strain gauge connected to a percutaneously inserted Cournand needle. Coronary sinus blood flow was measured by a thermodilution catheter flowmeter (5) inserted through the jugular vein

Regulation of postocclusive hyperemia by endogenously synthesized prostaglandins in the dog heart.

“…indonmethacin (5 X 10' M) has no effect on the calcium, sodium, or potassium fluxes of guinea pig heart muscle (26). The alpparent concentration of indomethacin in the heart-lung preparation in the present studies was either 2.8 X 10' M or 1.1 X 10' M but the effective concentration may have been considerably lower, since over 90% of indomethacin in canine plasma is protein bound (27 (5,29). Although it has not been proved, it has been speculated that the inhibition of the adenosine response is a result of the phosphodiesterase inhibition by the nmethylxanthines (30).…”

The Development of Tachyphylaxis to Electrical Stimulation in Guinea‐pig Ileal Longitudinal Muscles and the Possible Participation of Adenosine and Adenine Nucleotides

“…It Afonso, 1970;Sattin & Rall, 1970;Osswald, 1975;Ally & Nakatsu, 1976;Sawynok & Jhamandas, 1976;Okwuasaba et al, 1977). In contrast, dipyridamole and hexobendine have been shown to potentiate the inhibitory effect of adenosine and adenine nucleotide in the heart, intestine and trachea (Stafford, 1966;Kolassa, Pfleger & Rummel, 1970; At arrow, theophylline 30 gM was added to the superfusion solution.…”

Coronary vasodilator responses to hypoxia before and after aminophylline

“…Ainophylline was found to reduce by 50-75 % coronary vasodilator effects of adenosine administered i.v. or into the coronary artery (Afonso, 1970;Afonso & O'Brien, 1970). Although the intimate mechanism of this inhibitory action is not known, it has been suggested that aminophylline might act on the myocardium, or coronary vascular smooth muscle to produce this effect.…”