Cardiovascular and Sympathetic Effects of Leukotriene D₄ in Renovascular and Spontaneously Hypertensive Rats

Abstract

Leukotriene D₄ (LTD₄), a constituent of slow-reacting substance of anaphylaxis (SRS-A), elicits a pressor response followed by prolonged hypotension in spontaneously hypertensive (SHR) but not in Wistar-Kyoto (WKY) rats. In order to investigate whether the depressor response to LTD₄ in SHR rats is related to hypertension itself, we have studied the cardiovascular and sympathetic effects of LTD₄ in 1-kidney, 1-clip hypertensive rats and 1-kidney, normotensive rats. In all groups of conscious rats, intra-arterial administration of LTD₄ (0.2 − 20μg/kg) caused dose-dependent pressor responses of similar degree except in WKY rats, which responded less. Only SHR rats developed a significant and progressive hypotension (−58 ± 5 mm Hg) following pressor phase. In all but WKY rats, the response phase was attended by an increase in plasma levels of norepinephrine and epinephrine. Only SHR rats showed marked and persistent hemoconcentration following pressor effect.

Thus, depressor response of SHR rats to systemic administration of LTD₄ does not appear to be merely due to the magnitude of blood pressure elevation and may in part result from microcirculatory changes not present in other hypertensive rats.

Key Words:

• Leukotriene D₄
• Blood pressure
• Heart rate
• Catecholamines
• Renovascular
• Spontaneously hypertensive rats