Hormone selective lipase activation in the isolated rabbit heart

Area of Science:

• Biochemistry
• Cardiovascular Physiology
• Pharmacology

Background:

• Prostaglandins (PGs) play crucial roles in cardiovascular function.
• Lipase activity is central to prostaglandin biosynthesis.
• Understanding fatty acid mobilization is key to controlling PG production.

Purpose of the Study:

• To investigate the mechanisms of prostaglandin synthesis and release in the isolated perfused rabbit heart.
• To determine the role of specific fatty acids, particularly arachidonic acid, in bradykinin-stimulated PG production.
• To compare the effects of bradykinin stimulation with ischemia on fatty acid release and PG biosynthesis.

Main Methods:

• Utilized an isolated perfused rabbit heart model.
• Infused [14C]-labelled fatty acids (arachidonate, linoleate, oleate, palmitate) into the heart preparation.
• Stimulated hearts with bradykinin and induced ischemia.
• Measured bioassayable PGs and quantified the release of labelled fatty acids from phospholipids.

Main Results:

• Bradykinin stimulation selectively released [14C]-arachidonic acid, but not other fatty acids, from cardiac phospholipids for PG biosynthesis.
• Incorporation of fatty acids into cardiac phospholipids showed positional specificity, with arachidonate primarily at the 2-position of phosphatidylcholine.
• Ischemia induced non-selective release of fatty acids, including oleic and arachidonic acid, with a higher ratio of arachidonic acid to PG produced compared to bradykinin stimulation.

Conclusions:

• Bradykinin-induced prostaglandin synthesis involves the specific activation of lipases that mobilize arachidonic acid from cardiac phospholipids.
• Ischemia activates tissue lipases non-selectively, leading to a different pattern of fatty acid release and prostaglandin production compared to bradykinin.
• Distinct enzymatic mechanisms govern prostaglandin biosynthesis under hormonal stimulation versus ischemic conditions.