Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins.
To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE2, prostacyclin derivative 6kPGF1 alpha, and thromboxane [Tx] derivative TxB2). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE2 did not increase in angiotensin rats; however, both 6kPGF1 alpha and TxB2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 micrograms/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF1 alpha or TxB2. Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG.
Luft
F C
FC
Department of Physiology, University of Heidelberg, FRG.
Wilcox
C S
CS
Unger
T
T
Kühn
R
R
Demmert
G
G
Rohmeiss
P
P
Ganten
D
D
Sterzel
R B
RB
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012044:Regression Analysis; D013153:Splanchnic Nerves / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D000804:Angiotensin II; D000450:Aldosterone; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D008729:Methoxamine; D015232:Dinoprostone