Investigation of the mechanisms by which chronic infusion of an acutely subpressor dose of angiotensin II induces hypertension.
The mechanisms by which chronic infusion of an initially subpressor low dose of angiotensin II (ANG II) causes a progressive and sustained hypertension remain unclear. In conscious sheep (n = 6), intravenous infusion of ANG II (2 microg/h) gradually increased mean arterial pressure (MAP) from 82 +/- 3 to 96 +/- 5 mmHg over 7 days (P < 0.001). This was accompanied by peripheral vasoconstriction; total peripheral conductance decreased from 44.6 +/- 6.4 to 38.2 +/- 6.7 ml.min(-1).mmHg(-1) (P < 0.001). Cardiac output and heart rate were unchanged. In the regional circulation, mesenteric, renal, and iliac conductances decreased but blood flows were unchanged. There was no coronary vasoconstriction, and coronary blood flow increased. Ganglion blockade (125 mg/h hexamethonium for 4 h) reduced MAP by 13 +/- 1 mmHg in the control period and by 7 +/- 2 mmHg on day 8 of ANG II treatment. Inhibition of central AT(1) receptors by intracerebroventricular infusion of losartan (1 mg/h for 3 h) had no effect on MAP in the control period or after 7 days of ANG II infusion. Pressor responsiveness to incremental doses of intravenous ANG II (5, 10, 20 microg/h, each for 15 min) was unchanged after 7 days of ANG II infusion. ANG II caused no sodium or water retention. In summary, hypertension due to infusion of a low dose of ANG II was accompanied by generalized peripheral vasoconstriction. Indirect evidence suggested that the hypertension was not neurogenic, but measurement of sympathetic nerve activity is required to confirm this conclusion. There was no evidence for a role for central angiotensinergic mechanisms, increased pressor responsiveness to ANG II, or sodium and fluid retention.
Hood
S G
SG
Howard Florey Institute, Univ of Melbourne, Parkville, Victoria, Australia.
Cochrane
T
T
McKinley
M J
MJ
May
C N
CN
D000804:Angiotensin II / Q000008:administration & dosage* / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006973:Hypertension / Q000139:chemically induced*; D019808:Losartan / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012756:Sheep
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019808:Losartan