The polymorphonuclear leukocyte contributes to the development of hypertension in the Sabra rat.
BACKGROUND
We previously showed that priming of the polymorphonuclear leukocyte (PMNL), inflammation and oxidative stress antecede the development of hypertension in the Sabra rat model of hypertension. The actual role of PMNLs and PMNL-mediated oxidative stress and inflammation in the development of hypertension in this model has remained, however, unresolved.


OBJECTIVE
The aim of our study was to test the hypothesis that PMNLs and that the PMNL-associated NADPH oxidase contribute to the development of hypertension in the Sabra rat model.


METHODS
To determine the contribution of the PMNL to the development of hypertension, we depleted Sabra hypertension-prone (SBH/y) animals from PMNLs with an anti-PMNL antibody, salt-loaded them and monitored their blood pressure over a period of 30 days. To determine the contribution of the NADPH oxidase on the development of hypertension, we inhibited the activity of this enzyme with phenylarsine oxide or apocynin in SBH/y rats while salt-loading the animals and followed the course of their blood pressure over 60 days.


RESULTS
PMNL depletion attenuated significantly the development of hypertension in SBH/y rats. Inhibition of NADPH oxidase with phenylarsine oxide and apocynin markedly inhibited the development of hypertension in SBH/y rats, as well as decreased the rate of superoxide release, the level of PMNL CD11b and the PMNL count.


CONCLUSIONS
These data are consistent with a significant contribution of PMNLs to the development of hypertension, and suggest that the mechanism may be related, at least in part, to PMNL-mediated oxidative stress and inflammation.
Mazor
Rafi
R
Eliachar Research Laboratory, Western Galilee Hospital, Naharyia, Israel. mrafi@tx.technion.ac.il
Kristal
Batya
B
Cohen-Mazor
Meital
M
Yagil
Chana
C
Yagil
Yoram
Y
Sela
Shifra
S
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D039481:CD11b Antigen / Q000097:blood; D004195:Disease Models, Animal; D006973:Hypertension / Q000209:etiology*; D007958:Leukocyte Count; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000502:physiology; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D051381:Rats
D000098:Acetophenones; D039481:CD11b Antigen; C056165:acetovanillone; D019255:NADPH Oxidases