A mechanism of tolerance to the antihypertensive effect of ganglionic blocking agents in rats.

Functional tolerance was demonstrated to the antihypertensive effect of chlorisondamine Cl (Ecolid), a noncompetitive autonomic ganglion blocking agent, when administered chronically in increasing doses to spontaneously hypertensive rats (SHR), and normotensive Wistar-Kyoto (WKY) rats. Concomitant administration of atropine SO4 restored the hypotensive response to chlorisondamine without increasing its serum concentration. Atropine had no effect on the blood pressure of chlorisondamine-naive animals. No qualitative differences in therapeutic response were observed between the SHR and WKY rats. The results support the hypothesis that tolerance to the antihypertensive action of ganglionic blocking agents may be mediated by an activation of an alternate compensatory sympathetic ganglionic muscarinic pathway. It is speculated that this secondary pathway does not contribute to the hypertension in the SHR model.