Relationships among alterations in renal membrane sodium transport, renin and aminopeptidase M activities in genetic hypertension.
Rats of the Milan Hypertensive Strain (MHS) may be considered a useful model for understanding the genetic molecular mechanism underlying a primary form of hypertension in at least a subgroup of patients. Many differences between MHS and its normotensive control strain (MNS) were found at the organ, cellular and biochemical level. In the present investigation renal cell membrane proteins (BBMV) were analysed by two-dimensional electrophoresis and a difference between MHS and MNS was shown in a polypeptide of 32 kDa, subsequently identified as the C-terminal fragment of aminopeptidase M (APM). The activity of the enzyme was higher in MHS. Genetic relationships between this enzyme and the other biochemical cellular abnormalities of MHS, namely sodium transport in BBMV and renin activity in kidney cortex were investigated in MHS, MNS and in two inbred recombinant strains. This analysis showed that faster sodium transport, low kidney levels of renin and hypertension, but not differences in two-dimensional electrophoretic pattern and in aminopeptidase M activity, cosegregated in recombinant strains. These results are consistent with the hypothesis that the faster sodium transport can be considered a primary cellular abnormality responsible for hypertension in MHS and that the aminopeptidase difference is not involved in the cellular abnormalities.
Salardi
S
S
Prassis Istituto di Ricerche Sigma Tau, Settimo, Milanese, Italy.
Falchetto
R
R
Troffa
C
C
Parenti
P
P
Barber
B R
BR
Pastore
S
S
Glorioso
N
N
Bianchi
G
G
D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure; D018826:CD13 Antigens; D015180:Electrophoresis, Gel, Two-Dimensional; D006977:Hypertension, Renal / Q000235:genetics*; D007672:Kidney Cortex / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D012964:Sodium; D000626:Aminopeptidases; D018826:CD13 Antigens; D012083:Renin