Complex Abnormalities in Baroreflex Function in Patients with Monogenic Hypertension and Neurovascular Contact
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.