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Renal Haemodynamics are not Related to Genotypes in Offspring of Parents with Essential Hypertension

Department of Nephrology, Aarhus University Hospital, Aarhus, Denmark

Jens Kristian Madsen

Department of Medicine, Viborg County Hospital, Viborg, Denmark

Hans Erik Hansen

Department of Nephrology, Aarhus University Hospital, Aarhus, Denmark

Laura Zagato

Division of Nephrology, Dialysis and Hypertension, University 'Vita e Salute' San Raffaele Hospital, Milano, Italy

Erik Frandsen

Department of Clinical Physiology and Nuclear Medicine, Glostrup University Hospital, Denmark

Giuseppe Bianchi

Division of Nephrology, Dialysis and Hypertension, University 'Vita e Salute' San Raffaele Hospital, Milano, Italy

Michael John Mulvany

Department of Pharmacology, University of Aarhus, Aarhus, Denmark, mm{at}farm.au.dk

Introduction. The pathogenesis of essential hypertension (EH) has a major genetic component and is associated with renal abnormalities. Normotensive offspring of hypertensive parents are likely to develop EH and are a suitable population for identifying possible relations between genetic and renal abnormalities.

Methods. We investigated if renin-angiotensin-aldosterone system associated genotypes (angiotensinogen [M235T] and ACE [I/D]) are related to blood pressure (BP), renal haemodynamics and sodium excretion in sex and age-matched (18—35 years) healthy Caucasian offspring of either two parents with EH (n=101, EH-offspring) or two normotensive parents (n=50, controls). The alpha-adducin polymorphism (G460W) was also investigated.

Results. Compared to controls, BP, heart rate, renal vascular resistance (RVR) and urinary sodium excretion were, respectively, 5%, 7%, 15% and 20% higher in EH-offspring. In controls, the TT-genotype of the M235T angiotensinogen polymorphism was associated with higher BP and higher plasma angiotensinogen. By contrast, in EHoffspring the TT-genotype was associated with lower BP and unchanged plasma angiotensinogen. Plasma angiotensinogen correlated positively with BP in EH-offspring, with a similar tendency (p=0.08) in controls. The distributions of the three candidate polymorphisms were similar in EH-offspring and controls. There were no associations between any of the polymorphisms and any of the renal parameters measured.

Conclusion. The markedly greater RVR, proportionally larger than the greater BP, supports a role for RVR in the pathogenesis of EH. The lack of association between the candidate polymorphisms and the investigated parameters, even in this homogenous and for hypertension strongly predisposed group, suggests that the polymorphisms investigated do not play important roles in the pathogenesis of hypertension.

Key Words: Blood pressure • Genetics • Haemodynamics • Offspring

Journal of Renin-Angiotensin-Aldosterone System, Vol. 7, No. 1, 47-55 (2006)
DOI: 10.3317/jraas.2006.006


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