BACKGROUND A 60 member Turkish kindred with autosomal dominant hypertension, which cosegregates completely with brachydactyly and short stature, was studied. Affected people have severe hypertension ...and generally die of stroke by the age of 50. The hypertension closely resembles essential hypertension and, accordingly, the mechanisms of blood pressure elevation are unknown. The gene responsible was mapped to chromosome 12p. METHODS All 29 affected family members underwent a basic physical examination and funduscopy. Other than markedly elevated blood pressures and the residua of stroke in a few subjects, the apparent lack of end organ damage was striking, including the normal appearing fundi. Five affected individuals were studied in a clinical research unit study. All underwent a complete ophthalmological examination. Fluorescein angiograms were obtained in three subjects. RESULTS Systolic blood pressures ranged from 170 to 250 mm Hg, while diastolic blood pressures ranged from 100 to 150 mm Hg in affected individuals. In all affected subjects, the fundi were only minimally altered or clinically normal. All three fluorescein angiograms were normal. Despite severe hypertension since childhood the patients showed no signs of hypertensive retinopathy. CONCLUSIONS The absence of hypertensive retinopathy in this novel form of inherited hypertension is due to an altered structure of retinal arteriolar walls or some other protective mechanism. Since evidence of end organ damage is scarce in other organs as well, the protective mechanism appears to be generalised.
Abstract only P53 We have shown that autosomal-dominant hypertension with brachydactyly regularly features brainstem neurovascular compression (NVC). To seek mechanisms by which NVC could influence ...blood pressure, we conducted extensive autonomic tests in 5 affected persons (18-34 yrs.). Cold pressor testing, hand-grip testing, and upright posture all increased BP excessively. Baseline muscle sympathetic nerve activity was 15±4.6 bursts/min in patients, 12±6 bursts/min in normotensive controls, and 14±9 bursts/min in borderline hypertensive controls (ns). The increase in nerve traffic during cold pressor testing was not excessive. Urinary norepinephrine excretion was 19±4.0 μg/24 hours (normal range 23-105 μg/ 24 hours). Blood pressure during ganglionic blockade was134±4.9/ 82±4.1 mmHg in patients and 90±6/49±2.4 mmHg in controls (p<0.05). In patients, plasma vasopressin concentration changed from 0.47±0.03 pg/ml at baseline to 0.84±0.23 pg/ml during ganglionic blockade. In contrast, in control subjects, plasma vasopressin concentration increased profoundly from 1.6±0.17 pg/ml at baseline to 39±13 pg/ml during ganglionic blockade. The phenylephrine dose that increased SBP 12.5 mmHg was 8.0±2.0 μg in patients and 135±35 μg in control subjects before ganglionic blockade (p<0.01). During ganglionic blockade, the dose of phenylephrine that increased SBP 12.5 mmHg was 5.4±0.4 μg in patients and 13±4.8 μg in control subjects. The baroreflex slope was 9.4±1.6 msec/mmHg. We conclude that in these patients, basal BP was increased even during interruption of sympathetic and parasympathetic nerve traffic. However, sympathetic stimuli caused an excessive increase in BP. This excessive response cannot be explained by increased sympathetic nerve traffic or increased vascular sensitivity. Instead, we suggest that the ability of the baroreflex to buffer changes in blood pressure is severely impaired despite retained heart rate control.
BACKGROUNDProtein-losing enteropathy (PLE) is a severe complication of the univentricular Fontan circulation and associated with disturbances in salt and water homeostasis. Fontan patients with PLE ...have a poor prognosis, with increased morbidity and mortality. Due to limited therapeutic strategies, patients are often treated only symptomatically. METHODSWe report our first experience of Tolvaptan (TLV) treatment in a Fontan patient with PLE, severe volume retention and hyponatraemia, refractory to conventional diuretic therapy. In addition to clinical parameters, we monitored drug effects including tissue sodium and volume status via serial 23Na-magnetic resonance imaging (23Na-MRI) and bioimpedance spectroscopy compared with age-matched controls. RESULTS23Na-MRI identified elevated tissue sodium, which decreased under TLV treatment, as well as volume status, while serum sodium increased and the patient's symptoms improved. During long-term treatment, we were able to differentiate between sodium and volume status in our patient, suggesting that TLV uncoupled body sodium from water. CONCLUSIONTLV in addition to loop diuretics improved clinical symptoms of PLE and lowered tissue sodium overload. Long-term effects should be further evaluated in Fontan patients.
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