The present invention relates to the unexpected finding that vessels smaller than even the smallest arteries (i.e. arterioles) thicken, become dysfunctional and cause end organ damage to tissues as diverse as the brain and the kidney. Methods are provided to improve the structure and function of arterioles and to preserve the function of end organs such as the brain and kidney. In various embodiments the methods involve administering to a mammal in need thereof “D” or “L” class A amphipathic helical peptides.