Reduced alpha adrenergic mediated contraction of renal preglomerular blood vessels as a function of gender and aging.
As human males age, a decline in baroreflex-mediated elevation of blood pressure occurs due, at least in part, to a reduction in alpha-1 adrenergic vasoconstrictor function. Alpha adrenergic constriction is mediated by guanosine triphosphate binding Protein (G Protein) coupled signaling pathways. Alpha-1 A/C, B, and D adrenergic receptor expressions, measured by GeneChip array, are not reduced during aging in renal blood vessels of male or female rats. Alpha-1 A GeneChip expression is greater, at all ages studied, in females than in males. Prazosin binding by alpha-1 adrenergic receptors is greater in young adult female rats than in young adult male rats; however, it is reduced with aging in both male and female rats. G alpha q GeneChip expression declines while expression of adrenergic receptor kinase (GRK2) and tyrosine phosphatases (TyrP) increase with aging in male rats. The declines in alpha-1 adrenergic receptor binding and G alpha q expression and also the increases in GRK2 and TyrP expression likely relate to the age-related decline of vasoconstriction in male rats. The information that the expression of alpha-1 A adrenergic receptors is greater in female rats and (GRK2) expression does not increase during aging could relate to the gender differences in vasoconstrictor function with aging. Gene therapy to ameliorate the age-related decline in renal function could possibly reduce the need for renal dialysis. Signaling pathways such as those reviewed herein may provide an outline of the molecular pathways needed to move toward successful renal gene therapy for aging individuals.
Passmore
John C
JC
Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA. jcpass01@gwise.louisville.edu
Joshua
Irving G
IG
Rowell
Peter P
PP
Tyagi
Suresh C
SC
Falcone
Jeff C
JC
D000375:Aging / Q000502:physiology*; D000818:Animals; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D012079:Renal Circulation / Q000502:physiology*; D012727:Sex Characteristics; D015398:Signal Transduction
D018340:Receptors, Adrenergic, alpha-1