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

Abstract

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.

• Authors: S Seto, S Kitamura, S Nagao, M Nonaka, M Akahoshi, K Yano
• Journal: Brain research (Brain Res) Vol. 906 Issue 1-2 Pg. 164-9 (Jul 06 2001) ISSN: 0006-8993 [Print] Netherlands
• PMID: 11430874 (Publication Type: Journal Article)

Chemical References

• Carrier Proteins
• Diuretics
• Ganglionic Blockers
• Angiotensin II
• Hexamethonium
• Amiloride
• Sodium
• Norepinephrine

Topics

• Amiloride (pharmacology)
• Angiotensin II (pharmacology)
• Animals
• Blood Pressure (drug effects, physiology)
• Body Weight (drug effects, physiology)
• Brain (drug effects, growth & development, physiopathology)
• Carrier Proteins (drug effects, metabolism)
• Diuretics (pharmacology)
• Ganglionic Blockers (pharmacology)
• Hexamethonium (pharmacology)
• Hypertension (drug therapy, genetics, physiopathology)
• Male
• Norepinephrine (pharmacology)
• Rats
• Rats, Inbred SHR (genetics, growth & development, metabolism)
• Rats, Inbred WKY (genetics, growth & development, metabolism)
• Sodium (metabolism)
• Sympathetic Nervous System (drug effects, growth & development, physiopathology)
• Water-Electrolyte Balance (drug effects, physiology)