ROK and RSK2-kinase pathways differ between senescent human renal and mesenteric arteries

Area of Science:

• Cardiovascular Physiology
• Vascular Biology
• Aging Research

Background:

• Small arteries regulate blood flow through vasoconstriction, with mechanisms varying by organ.
• Advanced age can alter vascular function and contribute to cardiovascular diseases.

Purpose of the Study:

• To investigate the impact of advanced age on vasoconstriction regulation in human kidney and mesenteric small arteries.
• To compare age-related changes in vascular tone and signaling pathways between these two vascular beds.

Main Methods:

• Isolated human intrarenal (h-RA) and mesenteric arteries (h-MA) from elderly patients were studied using small vessel myography and western blot.
• Murine intrarenal (m-IAs) and mesenteric arteries (m-MA) from young and aged mice were also analyzed.

Main Results:

• Human intrarenal arteries exhibited higher stretch-induced tone and α1-adrenergic reactivity than mesenteric arteries.
• Rho-kinase (ROK) inhibition more effectively reduced tone in h-RA, indicating greater ROK dependence.
• Increased phosphorylation of MYPT1 and RSK2 was observed in h-RA, suggesting altered signaling pathways.
• Aged mouse interlobar arteries showed increased tone and RSK2 phosphorylation compared to young mice.

Conclusions:

• Human intrarenal arteries display greater Rho-kinase dependence in vasoconstriction compared to mesenteric arteries.
• Activation of ribosomal S6-kinase II (RSK2) may contribute to age-related dysregulation of intrarenal artery tone.
• Mesenteric arteries undergo age-related remodeling that reduces their contractile response to α1-adrenergic stimulation.