Date of Award
Master of Science (MS)
Sprague-Dawley rats of either sex, weighing 300 to 500g, were anesthetized with urethane (2-3mg/g). The hearts were rapidly removed and placed in a dish containing cold Krebs-Hensleit buffer (pH 7.2± .01) and continuously oxygenated with 95% oxygen, 5% carbon dioxide. The atria were cleared of as much extraneous tissue as possible and placed in an organ bath containing Krebs-Hensleit solution which was maintained at 31.0± .05 C and aerated with 95% oxygen, 5% carbon dioxide The effects of substance P (1 X 10-5 M to 4 X 10-5 M) and nicotine (1 X 10-5 M to 4 X 10-5 M) on atrial contractility were tested by the addition of these drugs to the organ bath. Contractions were recorded with a desk model DMP-4B Physiograph. The expected biphasic response to nicotine was observed at all concentrations tested. Substance P produced a direct inhibitory effect on atria contractility. This negative inotropic response to substance P was significant at all concentrations tested and occurred within a few beats (about 3 to 5 beats) from the addition of the drug to the bath. The negative effect of substance P was neither blocked by hexamathonium chloride (a nicotinic blocker) nor by atropine sulfate (a muscarinic blocker). No significant chronotropic response to substance P was observed. A control used in order to determine whether the acidified medium in which substance P was dissolved had itself any atrial effects produced no change in either rate or force of contraction. No positive inotropic response to nicotine was observed in the presence of substance P. It is not clear whether the negative effect of nicotine occurred in the presence of substance P because substance P itself produced an immediate inhibitory effect on atrial contractility. It is postulated that substance P liberated from pain-associated fibers in the heart might have a modifying action on the heart. The functional role, if any, for substance P producing a direct negative inotropy during episodes of cardiac pain has yet to be elucidated. However, such direct negative inotropy may be protective by counteracting excitability produced by catecholamines released from adrenals during cardiac pain episodes.
Ekeze, Tobias E., "Effects of Substance P on Nicotine-Induced Cholinergic Transmissions and Contractility in Isolated Rat Atrial Preparations" (1987). Biology Master’s Theses. 17.