Enhanced renal function in bradykinin B(2) receptor transgenic mice

Area of Science:

• Physiology
• Endocrinology
• Pharmacology

Background:

• The tissue kallikrein-kinin system regulates arterial pressure and renal function.
• Bradykinin B(2) receptors play a role in this system.

Purpose of the Study:

• To investigate the role of B(2) receptors in renal function using a transgenic mouse model.
• To analyze the effects of B(2) receptor overexpression on renal hemodynamics and electrolyte excretion.

Main Methods:

• Created transgenic mice overexpressing the human bradykinin B(2) receptor.
• Analyzed urinary excretion, renal blood flow, glomerular filtration rate, and serum/urinary electrolyte concentrations.
• Measured urinary and renal tissue levels of cGMP, cAMP, and kinins.
• Examined renin-angiotensin system component expression via Northern blot.

Main Results:

• Transgenic mice exhibited lifetime hypotension, increased urine output, potassium excretion, and pH.
• Renal blood flow and glomerular filtration rate were significantly elevated.
• Urinary and renal cGMP and cAMP levels increased, while urinary kinin levels remained unchanged.
• Hepatic angiotensinogen expression was upregulated, but renal renin and pulmonary ACE mRNA levels were unaltered.

Conclusions:

• Overexpression of B(2) receptors leads to hypotension and enhanced renal function.
• The effects are mediated by the nitric oxide-cGMP and cAMP signal transduction pathways.
• The renin-angiotensin system shows altered hepatic expression but not renal or pulmonary components.