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Aims: To determine whether initiation of treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARBs) is associated with a subsequent reduction in haemoglobin in the general population. Methods: We undertook a national cohort study over a 13‐year period (2004–2016), using routine primary healthcare data from the UK Clinical Practice Research Datalink. We compared ACEI/ARB initiation with calcium channel blocker (CCB) initiation, to minimise confounding by indication. We included all first ACEI/ARB or CCB prescriptions in adults with at least 1 haemoglobin result in the 12 months before and 6 months after drug initiation. Our primary outcome was a ≥1 g/dL haemoglobin reduction in the 6 months after drug initiation. Results: We examined 146 610 drug initiation events in 136 655 patients. Haemoglobin fell by ≥1 g/dL after drug initiation in 19.5% (16 936/86 652) of ACEI/ARB initiators and 15.9% (9521/59 958) of CCB initiators. The adjusted odds ratio of a ≥1 g/dL haemoglobin reduction in ACEI/ARB initiators vs CCB initiators was 1.15 (95% confidence interval 1.12–1.19). Conclusion: ACEI/ARBs are associated with a modest increase in the risk of a haemoglobin reduction. For every 100 patients in our study that initiated a CCB, 16 experienced a ≥1 g/dL haemoglobin decline. If the effect is causal, 3 additional patients would have experienced this outcome if they had received an ACEI/ARB. This may have implications for drug choice and monitoring for many patients in primary care. Further research could identify patients at higher risk of this outcome, who may benefit from closer monitoring. [ABSTRACT FROM AUTHOR]

Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compared the prevalence of single nucleotide polymorphisms ( SNPs) in genes of the renin-angiotensin system ( RAS) in a desert community of Indigenous Australians and in non-Indigenous Australians. The polymorphisms were angiotensinogen, AGT G-217A (rs5049); AGT G+174A (rs4762); Angiotensin II type 1 receptor, AGTR1 A+1166C (rs5186); angiotensin converting enzyme, ACE A-240T (rs4291), ACE T-93C (rs4292); renin, REN T+1142C (rs5706). They were measured using allelic discrimination assays. The prevalence of REN T+1142C SNP was similar in the two populations; 99% were homozygous for the T allele. All other SNPs were differently distributed between the two populations ( P < 0.0001). In non-Indigenous Australians, the A allele at position 204 of ACE rs4291 was prevalent (61.8%) whereas in the Indigenous Australians the A allele was less prevalent (28%). For rs4292, the C allele had a prevalence of 37.9% in non-Indigenous Australians but in Indigenous Australians the prevalence was only 1%. No Indigenous individuals were homozygous for the C allele of AGTR1 (rs5186). Thus the prevalence of RAS SNPs in this Indigenous Australian desert community was different from non-Indigenous Australians as was the prevalence of cytokine SNPs (as shown in a previous study). These differences may affect susceptibility to chronic renal and cardiovascular disease and may alter the efficacy of drugs used to inhibit the RAS. These studies highlight the need to study the pharmacogenetics of drug absorption, distribution, metabolism and excretion in Indigenous Australians for safe prescribing guidelines. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the roles of both angiotensin II (ANG II) receptors - type 1 (AT1Rs) and type 2 (AT2Rs) - separately and together in influencing hemodynamic effects of endogenously produced nitric oxide (NO) during postnatal development. In conscious, chronically instrumented lambs aged ~1 week (8 ± 1 days, N = 8) and ~6 weeks (41 ± 2 days, N = 8), systolic, diastolic, and mean arterial pressure (SAP, DAP, MAP) and venous pressure (MVP), renal blood flow (RBF), and renal vascular resistance (RVR) were measured in response to the l-arginine analog, l-NAME after pretreatment with either the AT1R antagonist, ZD 7155, the AT2R antagonist, PD 123319, or both antagonists. The increase in SAP, DAP, and MAP by l-NAME was not altered by either ATR antagonist in either age group. The increase in RBF after l-NAME was, however, altered by both ATR antagonists in an age-dependent manner, which was mediated predominantly through AT2Rs in newborn lambs. These findings reveal that there is an age-dependent interaction between the renin-angiotensin (RAS) and the NO pathway in regulating renal but not systemic hemodynamics through both ATRs, whereas AT2Rs appear to be important in the renal hemodynamic effects of NO early in life. [ABSTRACT FROM AUTHOR]