Apocynin activity in spontaneously hypertensive rats (SHR): preliminary studies in vivo.
An elevation in angiotensin II (Ang II) levels is a common occurrence in spontaneously hypertensive rats (SHRs). Infusions of Ang II and a high salt diet increase the activity of NADPH oxidase that stimulates superoxide anion (O(-2)) generation and increases the expression of certain subunits of NADPH oxidase. Apocynin, an NADPH oxidase inhibitor with antihypertensive effects, is able to inhibit the release of superoxide anion by inhibiting NADPH oxidase activity and blocking the migration of p47 phox to the mitochondrial membrane. The aim of our study was to evaluate the antihypertensive effects of apocynin in SHRs and Wistar rats (WKYs) using a micropuncture technique. After microperfusion of both the proximal and distal tubules, we found that SHRs treated with apocynin showed a decrease in the free-flow collection of the proximal tubule (PT), which was not affected in WKYs. Moreover, significant differences were not demonstrated in the distal tubule (DT), probably due a mechanism of compensation that occurs in the loop of Henle. In conclusion, it is possible that the mechanisms of reabsorption in the PT are controlled by the interactions of O(-2) and nitric oxide (NO). These data could suggest a higher activity of NADPH oxidase and increase in reactive oxygen species (ROS) production in the PT during hypertension.
Ciarcia
R
R
Dipartimento Strutture Funzioni e Tecnologie Biologiche, Facoltà di Medicina Veterinaria, Università degli Studi di Napoli Federico II, Napoli, Italy. roberto.ciarcia@unina.it
Damiano
S
S
Panico
C
C
Scanni
R
R
Fiorito
F
F
Florio
S
S
Welch
J W
JW
D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000098:Acetophenones; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; C056165:acetovanillone