Renal alpha 2a/d-adrenoceptor subtype function: Wistar as compared to spontaneously hypertensive rats

Area of Science:

• Nephrology
• Pharmacology
• Hypertension Research

Background:

• The alpha 2a/d-adrenoceptor subtype in the kidney influences solute excretion and blood pressure regulation.
• Genetic alterations in the alpha 2a/d-adrenoceptor subtype gene have been linked to hypertension in both rats and humans.

Purpose of the Study:

• To investigate if the alpha 2a/d-adrenoceptor subtype gene alteration in spontaneously hypertensive (SH) rats leads to attenuated osmolar clearance upon stimulation compared to normotensive Wistar rats.
• To determine if the alpha 2a/d-adrenoceptor subtype's functional response is intact in a model of acquired hypertension (one kidney-one clip, 1K-1C) compared to sham-operated controls.

Main Methods:

• Male Wistar, SH, 1K-sham, and 1K-1C rats were used.
• Rats were anesthetized and instrumented for blood pressure monitoring, fluid infusion, and urine collection.
• The alpha 2a/d-selective agonist guanfacine was infused intra-renally at varying doses.

Main Results:

• Guanfacine dose-dependently increased urine flow and sodium excretion, enhancing osmolar clearance in Wistar rats.
• In SH rats, guanfacine failed to alter urine flow, sodium excretion, or osmolar clearance.
• Both Wistar 1K-sham and 1K-1C rats showed increased urine flow and osmolar clearance in response to guanfacine, with no changes in blood pressure or creatinine clearance.

Conclusions:

• The kidney's alpha 2a/d-adrenoceptor subtype mediated increase in osmolar clearance is absent in genetically hypertensive SH rats.
• This functional defect is present in genetic hypertension but intact in acquired hypertension (1K-1C rats), suggesting a genetically determined defect in solute excretion modulation.
• Altered alpha 2a/d-adrenoceptor subtype gene and function may play a causal role in the pathogenesis of hypertension.