Platelet activating factor and one-kidney, one clip hypertension

Area of Science:

• Cardiovascular Research
• Renal Physiology
• Pharmacology

Background:

• The Goldblatt hypertensive rat model is used to study hypertension.
• A rapid reduction in blood pressure occurs after unclipping the renal artery in these rats.
• This blood pressure reduction was previously attributed to lipid mediators, potentially platelet activating factor.

Purpose of the Study:

• To investigate the role of platelet activating factor (PAF) in the blood pressure reduction observed in one-kidney, one clip Goldblatt hypertensive rats after unclipping.
• To determine if blocking the PAF receptor with WEB 2086 prevents the post-unclipping fall in blood pressure.

Main Methods:

• Administration of a PAF receptor antagonist (WEB 2086) intravenously to hypertensive rats before unclipping.
• Measurement of mean arterial blood pressure changes in antagonist-treated rats and saline-treated control rats.
• Confirmation of WEB 2086's efficacy in blocking exogenous PAF-induced hypotension and serotonin release.

Main Results:

• WEB 2086 administration did not significantly alter the blood pressure fall after unclipping.
• Blood pressure decreased by 28% in WEB 2086-treated rats (181 to 125 mm Hg).
• Blood pressure decreased by 33% in saline-treated control rats (194 to 127 mm Hg).

Conclusions:

• Platelet activating factor is unlikely to be the primary mediator responsible for the rapid blood pressure reduction in this model.
• The observed hypotension is likely due to other, currently unidentified, renomedullary lipids.
• This study refutes the hypothesis implicating PAF in the resolution of Goldblatt-induced hypertension.