Changes in the Sensitivity of the External Iliac Artery to Specific Vasoconstrictors and Vasodilators Following Chronic Treatment with Reserpine, a Potent Antihypertensive Agent

Abstract

This project is designed to define the changes in sensitivity and responsiveness that occur in blood vessels (an external iliac artery) after the normal sympathetic nervous system tone to these- vessels is chemically interrupted with reserpine. By treating an animal with reserpine, the normal neurotransmitters (stimuli) that are involved in regulating blood vessel tone (blood pressure) are depleted, and this is how reserpine lowers blood pressure. Thus, since stimulus intensity is decreased, blood vessels will up regulate (increase) their reponsiveness. When removed from the animal and studied in an isolated tissue bath containing a physiological saline solution, these vessels were supersensitive to selective vasoconstrictor stimuli specifically norepinephrine and Bay K 8644. The results indicated that: 1) tissues from reserpine treated animals were selectively supersensitive to the normal neurotransmitter, norepinephrine and the selective potential-dependent Ca⁺⁺ channel activator, Bay K 8644; 2) D600, a Ca⁺⁺ entry blocker t eliminated the difference in sensitivity to norepinephrine; 3) no differences between treated and control were noted in the sensitivity to Ca⁺⁺, KCl, or histamine; 4) neither control nor reserpine treated vessels responded to beta adrenoceptor stimulation with isoproterenol; and 5) no differences in the sensitivity to the relaxing action of acetylcholine and nitroprusside were noted in vessels from treated and control animals. Therefore, a major portion of the enhanced sensitivity found in reserpine treated vessels is related to norepinephrine- induced activation of potential-dependent Ca⁺⁺ channels.