Pressor and hormonal responses to angiotensin I infusion in healthy subjects of different angiotensin-converting enzyme genotypes.
The effects of incremental infusion of angiotensin I on pressor and hormonal responses in relation to the angiotensin-converting enzyme (ACE) genotype were compared in healthy men of genotype DD (n = 8) and II (n = 8). The R(d)25 was the rate of angiotensin I infusion required to achieve a 25-mm Hg increase in diastolic pressure, and the R(s)25, that which caused a 25-mm Hg increase in systolic pressure. Changes in heart rate (HR25) were analysed at the time the R(d)25 was achieved. Serum ACE activity and plasma renin, angiotensin II, and aldosterone concentrations were measured at the start and end of the angiotensin I infusion. Serum ACE activity differed significantly between the genotypes with significantly higher mean values in DD subjects (46.3 +/- SEM 5.2 U/L) than II subjects (12.3 +/- 1.4 U/L; p < 0.001). Age, weight, and baseline blood pressure, heart rate, urinary sodium excretion, plasma renin, angiotensin II, and aldosterone concentrations did not differ between genotypes. The geometric mean infusion rates of angiotensin I required to achieve R(d)25 were 2.53 micrograms/min in II subjects and 2.67 micrograms/min in DD subjects (ratio of infusion rates, 0.95; 95% CI, 0.44-2.02; p > 0.05). The corresponding infusion rates for systolic blood pressure (R(s)25) were 4.47 micrograms/min in II subjects and 3.39 micrograms/min in DD subjects (ratio, 1.32; 95% CI, 0.49-3.55; p > 0.05). At the time of R(d)25, changes in heart rate from baseline were +1.2 beats/min for DD subjects and -9.5 beats/min for II subjects (diff II-DD = 10.7 beats/min; 95% CI, 6.7-14.8; p = 0.01). There were no differences in plasma renin, angiotensin, and aldosterone responses to angiotensin I infusion between the DD and II genotypes. We showed no difference in blood pressure or renin-angiotensin-aldosterone system responses to infusion of angiotensin I related to the deletion or insertion allele of the ACE gene polymorphism, but the study has insufficient power to exclude with certainty such differences. There was a significant difference between II and DD subjects in the chronotropic response to angiotensin I infusion.
Chadwick
I G
IG
University Department of Medicine & Pharmacology, Royal Hallamshire Hospital, Sheffield, England.
O'Toole
L
L
Morice
A H
AH
Yeo
W W
WW
Jackson
P R
PR
Ramsay
L E
LE
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000483:Alleles; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009842:Oligopeptides / Q000737:chemistry; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D012964:Sodium / Q000652:urine; D013056:Spectrophotometry, Ultraviolet; D044465:White People
D009842:Oligopeptides; D000804:Angiotensin II; D000450:Aldosterone; C038275:2-furanacryloyl-phenylalanyl-glycyl-glycine; D004247:DNA; D000803:Angiotensin I; D012964:Sodium; D007703:Peptidyl-Dipeptidase A; D012083:Renin