Nischarin Is Not the Functional I1 Imidazoline Receptor Involved in Blood Pressure Regulation.

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Molecular Biology

Background:

• Nischarin was hypothesized as the functional imidazoline receptor 1 (I1R).
• I1Rs are targeted by antihypertensive drugs like clonidine.
• The imidazoline binding site on nischarin was considered crucial for I1R function.

Purpose of the Study:

• To investigate if nischarin is the functional I1R.
• To evaluate the cardiovascular effects of a selective I1R agonist, LNP599, in nischarin mutant rats.

Main Methods:

• Cardiovascular effects of LNP599 (3 mg/kg IV) were assessed in anesthetized, ventilated wild-type and nischarin mutant rats.
• Nischarin mutant rats expressed a truncated nischarin lacking the putative imidazoline binding site.

Main Results:

• LNP599 caused significant hypotension and bradycardia in wild-type rats.
• Similar hypotensive and bradycardic responses to LNP599 were observed in homozygous and heterozygous nischarin mutant rats.
• Carbohydrate regulation was improved in nischarin mutant rats.

Conclusions:

• The hypotensive response to I1R activation is independent of the nischarin binding site.
• Nischarin is not the functional I1R; it is distinct from I1R.
• Nischarin plays a role in carbohydrate regulation.