Psychosocial stress induces tubulointerstitial nephritis unrelated to hypertension in CBA mice

Area of Science:

• Neuroscience
• Cardiovascular Science
• Nephrology

Background:

• Social interaction in complex environments can induce stress responses in mice.
• This stress can lead to hypertension and chronic tubulointerstitial nephritis.
• The sympathetic nervous system and the pituitary-adrenal axis are implicated in stress responses.

Purpose of the Study:

• To investigate the effects of social stress on blood pressure and kidney function in mice.
• To evaluate the efficacy of metoprolol, a beta-blocker, in mitigating stress-induced hypertension and nephritis.
• To explore the role of the pituitary-adrenal cortical system in the development of stress-related renal disease.

Main Methods:

• Mice were housed in complex population cages to induce social stress.
• Long-term administration of metoprolol was used to block sympathetic nervous system activity.
• Measurements included blood pressure, plasma renin, adrenal tyrosine hydroxylase, adrenal weight, and plasma corticosterone levels.

Main Results:

• Socially stressed mice developed hypertension and chronic tubulointerstitial nephritis.
• Metoprolol treatment normalized blood pressure and reduced stress markers like plasma renin and adrenal tyrosine hydroxylase.
• Despite effective sympathetic blockade, metoprolol did not decrease the incidence of nephritis.
• Stress-induced increases in adrenal weight and corticosterone persisted during metoprolol treatment.

Conclusions:

• Sympathetic blockade with metoprolol effectively controls stress-induced hypertension but not nephritis in mice.
• The pituitary-adrenal cortical system appears to be independent of sympathetic activity in this model.
• The persistent activation of the pituitary-adrenal cortical system may play a role in the development of stress-induced renal disease.