Contribution of central amiloride-sensitive transport systems to the development of hypertension in spontaneously hypertensive rats

This study was conducted to examine if central amiloride-sensitive transpor t systems are involved in the development and/or maintenance of hypertensio n in spontaneously hypertensive rats (SHR). Either amiloride (75 mug/60 mul /day) or artificial cerebrospinal fluid (aCSF, 60 mul/day) was infused cent rally (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, amilo ride 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 can celed after ganglionic block with hexamethonium (115+/-4 vs. 117+/-5 mmHg), Further, presser responsiveness to norepinephrine was augmented in amilori de 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 cumul ative sodium balance did not differ in the two groups. Intravenous administ ration of amiloride at the same dose did not attenuate the development of h ypertension. On the other hand. in maintenance phase, amiloride i.c.v. by t he 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 inv olved in the development, but not in the maintenance, of hypertension in SH R through the modulation of autonomic neural mechanisms. (C) 2001 Published by Elsevier Science B.V.