Leukotriene D4 inhibits cardiovascular responses to sympathetic stimulation, angiotensin and vasopressin in the pithed spontaneously hypertensive rats.

We have previously shown that high doses of leukotriene D4 (LTD4) induces hypotension in conscious and in pithed spontaneously hypertensive rats. The present study was designed to determine whether the hypotensive effect of LTD4 in spontaneously hypertensive rats is due to reduced sensitivity of peripheral blood vessels to pressor stimuli and/or reduced responsiveness of the sympatho-adrenomedullary system. To test these possibilities we examined the effect of spinal cord stimulation, vasopressin, norepinephrine and angiotensin II on blood pressure, heart rate and plasma catecholamines of pithed spontaneously hypertensive rats, before and after treatment with LTD4 (20 micrograms/kg i.v.), a dose which produces hypotension in conscious and pithed rats. LTD4 suppressed the pressor responses to spinal cord stimulation (50 V, 1 msec, for 1 min) at 0.3 and 3.0 Hz by 64% (P less than .001) and 71% (P less than .001), respectively, and the pressor and cardiac accelerating effects of systemic injections of norepinephrine. Plasma norepinephrine response to spinal cord stimulation at 3.0 Hz was significantly (P less than .05) reduced after administration of LTD4. The evoked release of epinephrine from the adrenal medulla was enhanced (+139%, P less than .05) by LTD4, but the tachycardia was blocked. The pressor responses to 0.1 and 1.0 microgram/kg of angiotensin II were blocked by 73% (P less than .05) and 70% (P less than .01), respectively. The pressor effects produced by vasopressin (0.03 and 0.1 microgram/kg) were also attenuated (by 83 and 80%, respectively) after LTD4 administration. The depressor effect of sodium nitroprusside (0.01-0.1 mg/kg) was also attenuated by LTD4. These data suggest that LTD4-induced hypotension involves severe interference with vascular smooth muscle responsiveness to all pressor agents.(ABSTRACT TRUNCATED AT 250 WORDS)