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Mads Damkjær


Persons with an arterial blood pressure (ABP) above 140/90 mmHg are said to have hypertension. Hypertension is probably the most important public health problem in the developed countries. It is common, asymptomatic and often leads to lethal complications if left untreated. In 90 – 95% of patients suffering from this condition no definable cause can be found. These patients are said to have essential hypertension. Due to the lack of a clearly identifiable pathogenesis of this disease the treatment is non‐specific, and carries with it a significant amount of minor side effects. These side effects coupled with the asymptomatic nature of the disease results in a relatively high noncompliance rate to treatment (50 to 60%). Identifying the pathogenesis could provide the basis for developing new more efficient treatment regimens. Essential hypertension is a disease frequently suggested to include sodium retention, and a volume dependent increase in ABP. The focus of this thesis is the interplay between the long‐term control of ABP and total body sodium (TBS) in normal physiology and in patients with essential hypertension. Mechanisms of normal sodium homeostasis.

Sodium balance is characterized by identity between intake and excretion over time. It is well established that TBS is a tightly regulated entity, yet the exact mechanisms linking changes in TBS to renal excretion are still unclear. It has been suggested that changes in renal medullary blood flow (MBF) may provide such a link between TBS and renal excretion. We have developed a novel method to measure renal MVF in humans (study II), and we then applied it to study acute changes in TBS (study III). Mechanisms of sodium homeostasis in patients with essential hypertension.

Patients with essential hypertension may retain sodium compared to normotensive controls. We examined if this could be due to an attenuated suppression of renin‐angiontensin‐aldosterone system (RAAS) (study IV). Furthermore we examined how much of the increase in systemic vascular resistance (SVR) in patients with essential hypertension is due to selective renal vasoconstriction.  

Conclusions We have proposed a novel method for non‐invasive observer independent quantification of renal medullary blood flow. By changing nitric oxide (NO) availability we also show that the method can be used to detect changes in medullary and cortical blood flow. During an intravenous sodium load urinary sodium excretion in normotensive healthy controls increased 3.7 fold. This increase occurred without measurable changes in renal MBF or ABP. Patients with essential hypertension have 15% higher systemic vascular resistance (SVR) than normotensive controls. Surprisingly, this is caused by a selective increase in renal vascular resistance. The patients furthermore have renal hypoperfusion and hypofiltration. Remarkably they excrete more sodium (exaggerated natriuresis) in response to an acute sodium load than controls. This despite identical dynamics of the RAAS.