G-proteins in essential hypertension: a study of human platelet plasma membranes.
OBJECTIVE
Guanine nucleotide regulatory (G) proteins act as key signal transducers for many hormones, growth factors and neurotransmitters, and have been shown to have an important influence on platelet function. As abnormal G-protein levels and activity have been reported in platelets from human non-insulin-dependent diabetics (NIDDM) we studied G-protein function in essential hypertension, a condition which is also associated with insulin resistance and in which abnormal platelet function has been reported.


METHODS
G-protein function was deduced from studies of adenylyl cyclase activity in platelet membrane preparations from 14 untreated essential hypertensives and 14 controls matched as far as possible for age and sex. Levels of G-protein subunits (Gs alpha, Gi alpha 2 and beta-subunits) were assessed by immunoblotting, using platelets from 15 subjects with untreated essential hypertension and 15 controls.


RESULTS
No changes in levels of G-proteins (Gs alpha, Gi alpha 2 and beta-subunits) were seen. However, in contrast to the observations in NIDDM, the studies of adenylyl cyclase function identified greater prostaglandin E1-stimulated activity in hypertensive platelet membranes than in controls (88.8 verus 72% stimulation, P = 0.018). This may have a physiological basis in protecting cells against a Ca2+ overload.


CONCLUSIONS
These data are in opposition to the theory that a common defect in G-proteins can explain the association between hypertension and NIDDM.
McLellan
A R
AR
MRC Blood Pressure Unit, Western Infirmary, Glasgow, UK.
Milligan
G
G
Houslay
M D
MD
Connell
J M
JM
D000262:Adenylyl Cyclases / Q000097:blood; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000097:blood*; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged
D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil