This study was conducted to examine if central
amiloride-sensitive transport systems are involved in the development and/or maintenance of
hypertension in spontaneously hypertensive rats (SHR). Either
amiloride (75 microg/60 microl/day) or artificial cerebrospinal fluid (aCSF, 60 microl/day) was infused centrally (i.c.v.) for 4 weeks to development (4-5-weeks-old) and maintenance (10-12-weeks-old) phases of
hypertension in SHR. In development phase,
amiloride i.c.v. (n=14) blunted the elevation of blood pressure (BP) compared to aCSF i.c.v. (n=9) (
amiloride vs. aCSF; after 3 weeks of i.c.v., 146+/-3 vs. 166+/-5 mmHg, P<0.001). The difference of BP at 3 weeks of i.c.v. was canceled after ganglionic block with
hexamethonium (115+/-4 vs. 117+/-5 mmHg). Further, pressor responsiveness to
norepinephrine was augmented in
amiloride i.c.v. rats (
amiloride, n=11 vs. aCSF, n=6; %Delta BP at 800 ng/kg/min.: 16.9+/-1.3 vs. 10.8+/-1.4 mmHg, P<0.05) and this augmentation disappeared after ganglionic block. Pressor responsiveness to
angiotensin II and cumulative
sodium balance did not differ in the two groups.
Intravenous administration of
amiloride at the same dose did not attenuate the development of
hypertension. On the other hand, in maintenance phase,
amiloride i.c.v. by the same protocol as in development phase had no effect on BP in SHR. Also,
amiloride i.c.v. did not affect BP in normotensive Wistar-Kyoto rats. These results suggest that central
amiloride-sensitive transport systems are involved in the development, but not in the maintenance, of
hypertension in SHR through the modulation of autonomic neural mechanisms.