Altered biochemical and functional responses in aorta from hypertensive rats.
Factors that lead to supersensitivity of vascular smooth muscle to norepinephrine during aldosterone-salt-induced hypertension in rats appear to reside beyond ligand-alpha-adrenergic receptor binding, which we have shown previously to be normal. The objective of this study was to determine whether significant shifts occur in the coupling between receptors and the production of putative second messengers. Measures of [3H]myo-inositol phosphates in aorta (endothelium removed) exhibited a concentration-dependent increase to norepinephrine, with the 50% response shifted significantly to the left in the hypertensive group (7.0 +/- 0.9 X 10(-7) M in 8 control rats vs 1.1 +/- 0.2 X 10(-7) M in 8 hypertensive rats; p less than 0.001). The production of [32P]phosphatidic acid was also shifted (6.5 +/- 2.5 X 10(-7) M in 16 control vs 1.9 +/- 0.8 X 10(-7) M in 12 hypertensive rats; p less than 0.05). The functional responses of 42K efflux and contraction to norepinephrine were also significantly shifted threefold to 15-fold in the hypertensive group (p less than 0.001), but the 50% response typically occurred at a 10 to 100 times lower concentration than that for the production of myo-inositol phosphates and phosphatidic acid. The amplification between receptor occupancy and functional responses apparently occurs beyond the production of phosphoinositide metabolites. The fivefold shift in the 50% response of biochemical end points for the hypertensive group accounted for most of the shift (sixfold) in the functional end points.(ABSTRACT TRUNCATED AT 250 WORDS)
Jones
A W
AW
Department of Physiology, University of Missouri, Columbia 65212.
Geisbuhler
B B
BB
Shukla
S D
SD
Smith
J M
JM
D000818:Animals; D001011:Aorta / Q000032:analysis / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013403:Sugar Phosphates / Q000096:biosynthesis*
D007295:Inositol Phosphates; D010712:Phosphatidic Acids; D011942:Receptors, Adrenergic, alpha; D013403:Sugar Phosphates; D011188:Potassium; D009638:Norepinephrine