Alpha 1 adrenergic receptor control of renal blood vessels during aging.
Aging humans and rats have a reduced renal vascular constriction response to stress, change in posture, or exercise. In this study, renal interlobar arteries from 9- (intermediate age) to 15-month-old (aging) male Wistar rats constricted less to alpha-adrenergic agonists than those of 4-month-old (young adult) rats. The reduced contraction to A61603 (alpha 1 A agonist) was similar to that to norepinephrine and phenylephrine. Therefore, it appears that the reduction in constriction is primarily related to alpha 1 A receptor stimulation. GeneChip microarray hybridization analysis of the interlobar arteries with the RAE 230A GeneChip indicated that there were no significant differences in gene expression for alpha 1 A/C, 1B, or 1D receptors between 4-month-old (young adult) and 1-year-old (aging) male Wistar rats. Competitive binding experiments (prazosin) revealed that maximal binding (Bmax, fmol/mg protein) of the alpha 1 receptors of interlobar arteries was reduced 25% by 10 months of age and 50% by 18+ months of age. Alpha 1 receptor-induced arterial constriction and prazosin binding were both down-regulated. The loss of receptor-initiated constriction likely includes down-regulation of maximum agonist binding by alpha 1 adrenergic receptors.
Passmore
John C
JC
Department of Physiology and Biophysics, School of Medicine, University of Louisville, KY 40292, USA. jcpass01@gwise.louisville.edu
Rowell
Peter P
PP
Joshua
Irving G
IG
Porter
James P
JP
Patel
Divyan H
DH
Falcone
Jeff C
JC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011224:Prazosin / Q000494:pharmacology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D012313:RNA; D011224:Prazosin