Development of histamine tachyphylaxis in the guinea-pig mesenteric artery

Histamine, norepinephrine and KCl each evoke contractile responses in isolated guinea-pig mesenteric artery. However, only the contractile response to histamine was characterized by acute desensitization or tachyphylaxis. The tachyphylaxis observed to histamine was independent of the time interval between successive administrations up to at least 1 hr. The histamine H1-receptor blocker, chlorpheniramine (10(-9) M), completely inhibited contractile responses to histamine (10(-5) M). In contrast, metiamide (10(-4) M), an H2-receptor blocker, potentiated contractions which were characterized by tachyphylaxis. Propranolol (10(-6) M), phentolamine (10(-6) M) and atropine (10(-6) M) affected neither the contractile response itself nor the tachyphylaxis to histamine (10(-5) M). Indomethacin (10(-5) M) and aspirin (3 X 10(-4) M) potentiated the initial contraction induced by histamine (10(-5) M) and completely abolished the tachyphylaxis. The response to the initial application of histamine (10(-5) M) was not affected by the reduction of [Ca++] to 0.25 mM or by diltiazem (10(-5) M) or verapamil (10(-5) M). The tachyphylaxis to histamine was, however, suppressed slightly but significantly by the reduction of [Ca++]o and by Ca++ antagonists. These results suggest that the development of tachyphylaxis to histamine in the isolated guinea-pig mesenteric artery may result from the production of prostaglandins which are sensitive to Ca++.