The 1166 A/C polymorphism of the angiotensin II type 1 receptor gene does not correlate with the blood pressure response to angiotensin II in patients with CHF

Whether the 1166 (A/C) polymorphism of the Angiotensin II (AII) type 1 receptor (AT1R) gene does correlate with increased vascular reactivity to AII is unclear. Accordingly we measured the blood pressure response to exogenous AII and determined the 1166A/C AT1R gene polymorphism in patients with Chronic Heart Failure (CHF). 40 patients with CHF and functional capacity compatible with NYHA class II-III were studied. All patients were genotyped for the 1166 A/C polymorphism. The frequency of the C allele was 0.2. Radial Artery Systolic Pressure (RASP) was non-invasively monitored using a Colins Pilot Monitor 9200. Ascending doses of AII were administered intravenously to increase RASP by 20 mmHg (AII Pd 20). Patients with CHF exhibited a 10-fold variability in their response to AII with Pd 20 ranging from 2.5 to 25 ng/kg. Patients with AA or AC/CC genotype, had similar AII Pd 20: 11.35 ± 1.18 vs. 13.21 ± 2.2 respectively (p = 0.42). Similarly, among the patients with decreased vascular reactivity who required ≥ 10 ng/kg of AII to achieve Pd 20 (n = 29), RASP response to 10 ng/kg of AII was comparable among patients with AA and AC/CC genotype 22.5 ± 2.8 vs. 21.9 ± 3.3 mmHg respectively (p = 0.9). In patients with CHF, the doses of AII required to increase BP by 20 mmHg demonstrate a 10-fold variability. The 1166A/C polymorphism of the AT1R gene does not account for the wide range of AII Pd 20. Factors other than 1166A/C polymorphism of the AT1R gene are likely to determine BP response to exogenous AII in CHF patients.