PMID- 8621203
OWN - NLM
STAT- MEDLINE
DCOM- 19960614
LR  - 20190722
IS  - 0194-911X (Print)
IS  - 0194-911X (Linking)
VI  - 27
IP  - 5
DP  - 1996 May
TI  - Alpha 2-adrenergic agonists increase cellular lactate efflux.
PG  - 1104-7
AB  - We reported previously that genetic polymorphisms of the alpha 2-adrenergic 
      receptor are associated with hyperinsulinemia, diabetes mellitus, and 
      hypertension in blacks. The evolutionary driving force for maintaining such 
      deleterious mutations in the black population is unknown. Recognizing that 
      vascular alpha 2-adrenergic receptors mediate cold-induced vasoconstriction and 
      that temperature maintenance is a primary thrust of cellular metabolism, we 
      postulated that vascular alpha 2-adrenergic receptors contribute significantly to 
      metabolic heat generation in homeotherms such as humans. Using aerobic lactate 
      production as an indicator of thermogenesis, we measured metabolic heat 
      production in HT29 cells that expressed the gene encoding human vascular alpha 
      2-adrenergic receptors. Epinephrine, an alpha 2-adrenergic receptor agonist, 
      increased net lactate efflux from 226 +/- 20 to 280 +/- 20 nmol/min (mean +/- SE) 
      (P = .06). Clonidine, a more specific alpha 2-adrenergic agonist, increased 
      lactate efflux from 110 +/- 6 to 156 +/- 8 nmol/min (P < .01). Similarly, in the 
      presence of physiological concentrations of glucose (5.5 mmol/L), insulin 
      increased lactate production from 123 +/- 6 to 175 +/- 10 nmol/min (P < .01). 
      Because differences in aerobic glycolysis may also explain the heat intolerance 
      and abnormal fuel homeostasis found in genetically hypertensive rats, we also 
      measured lactate production in cultured vascular smooth muscle cells isolated 
      from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive 
      control Wistar-Kyoto rats (WKY). Vascular smooth muscle cells from SHRSP had 
      significantly greater lactate efflux compared with cells from normotensive WKY 
      (296 +/- 4 versus 172 +/- 2 nmol/min, P < .001). These differences were not due 
      to abnormalities in glucose uptake, as lactate efflux was greater in SHRSP cells 
      compared with WKY cells when dextrose was replaced with equimolar concentrations 
      of fructose (230 +/- 6 versus 138 +/- 2 nmol/min, P < .001). alpha 2-Adrenergic 
      agonists increase lactate efflux in HT29 cells, and abnormalities in vascular 
      smooth muscle lactate metabolism in genetically hypertensive rats is independent 
      of altered glucose uptake. These data provide support for our hypothesis that 
      balanced polymorphisms of the alpha 2-adrenergic receptor could offer protection 
      against cold stress by increasing the thermogenic response associated with 
      aerobic lactate production.
FAU - Lockette, W
AU  - Lockette W
AD  - Division of Endocrinology, Wayne State University School of Medicine, Detroit, MI 
      48201, USA.
FAU - Kirkland, K
AU  - Kirkland K
FAU - Farrow, S
AU  - Farrow S
LA  - eng
GR  - HL-50849/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 0 (Insulin)
RN  - 0 (Lactates)
RN  - 33X04XA5AT (Lactic Acid)
RN  - MN3L5RMN02 (Clonidine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Adrenergic alpha-Agonists/*pharmacology
MH  - Animals
MH  - Body Temperature Regulation
MH  - Cells, Cultured
MH  - Cerebrovascular Disorders/genetics
MH  - Clonidine/pharmacology
MH  - Epinephrine/pharmacology
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Insulin/pharmacology
MH  - Lactates/*metabolism
MH  - Lactic Acid
MH  - Muscle, Smooth, Vascular/cytology/drug effects/metabolism
MH  - Rats
MH  - Rats, Inbred SHR/genetics
MH  - Rats, Inbred WKY
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
AID - 10.1161/01.hyp.27.5.1104 [doi]
PST - ppublish
SO  - Hypertension. 1996 May;27(5):1104-7. doi: 10.1161/01.hyp.27.5.1104.