Severely Impaired Baroreflex-Buffering in Patients With Monogenic Hypertension and Neurovascular Contact

Abstract

Background-We identified a family with a monogenic syndrome of hypertension, brachydactyly, and neurovascular contact of the brain stem. Neurovascular contact of the ventrolateral medulla may lead to arterial hypertension by interfering with baroreflex function. Methods and Results-In 5 patients with monogenic hypertension (18 to 34 years old), we conducted detailed autonomic function tests. Blood pressure during complete ganglionic blockade was 134Ϯ4.9/82Ϯ4.1 mm Hg and 90Ϯ6/49Ϯ2.4 mm Hg in patients and in control subjects, respectively. During ganglionic blockade, plasma vasopressin concentration increased 24-fold in control subjects and Ͻ2-fold in patients. In patients, cold pressor testing, hand-grip testing, and upright posture all increased blood pressure excessively. In contrast, muscle sympathetic nerve activity was not increased at rest or during cold pressor testing. The phenylephrine dose that increased systolic blood pressure 12.5 mm Hg was 8.0Ϯ2.0 g in patients and 135Ϯ35 g in control subjects before ganglionic blockade and 5.4Ϯ0.4 g in patients and 13Ϯ4.8 g in control subjects during ganglionic blockade. Conclusions-In patients with monogenic hypertension and neurovascular contact, basal blood pressure was increased even during sympathetic and parasympathetic nerve traffic interruption. However, sympathetic stimuli caused an excessive increase in blood pressure. This excessive response cannot be explained by increased sympathetic nerve traffic or increased vascular sensitivity. Instead, we suggest that baroreflex buffering and baroreflex-mediated vasopressin release are severely impaired.

Genetics of arterial hypertension and hypotension

“…Complete ganglionic blockade did not reduce hypertensive blood pressure values in young affected family members, suggesting that autonomic activity is not responsible for increases in basal blood pressure (Jordan et al 2000). Likewise, muscle sympathetic nerve activity during sympathetic stimulation was not different or even lower at rest and upon stress testing in affected subjects, arguing against an increased sympathetic nerve activity.…”

“…Similarly, the potency of the non-selective α-adrenoceptor-agonist phenylephrine to increase blood pressure was more than an order-ofmagnitude higher in the affected family members. Since the relative sensitivity to phenylephrine was distinctly reduced in these patients during ganglionic blockade-which also blocks the baroreceptor reflex-the authors concluded that an impaired ability of the baroreceptor reflex to compensate increases in blood pressure is a crucial abnormality in this type of monogenic hypertension (Jordan et al 2000).…”

Blood pressure variability and prognosis in acute ischemic stroke with vascular compression on the rostral ventrolateral medulla (RVLM)

“…It has been reported that baroreflex buffering and baroreflex-mediated vasopressin release are severely impaired in patients with RVLM vascular compression. 7 When the impaired baroreflex is associated with RVLM vascular compression, blood pressure variability may increase with increased sympathetic nerve activity. It has been suggested that restoration of baroreflex sensitivity may prevent stroke in the animal model.…”

“…It is currently hypothesized that chronic stimulation of this region with vascular compression can cause constitutive activation of the sympathetic nervous system and the development of hypertension. 7,8 More than 80% of acute stroke patients have elevated blood pressure. Several days following the incidence of stroke, however, the blood pressure in these patients returns to baseline levels.…”

Baroreflex Buffering and Susceptibility to Vasoactive Drugs

“…1,19,20 We developed a new strategy to assess baroreflex buffering by comparing the pressor effect of phenylephrine on blood pressure before and during ganglionic blockade. 16 The pressor effect of phenylephrine before ganglionic blockade is a function of vascular responsiveness and buffering by the baroreflex. Because the baroreflex loop is interrupted at the level of autonomic ganglia, phenylephrine sensitivity during trimethaphan infusion is mainly influenced by systemic vascular responsiveness.…”