Severely impaired baroreflex-buffering in patients with monogenic hypertension and neurovascular contact.
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.


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 134+/-4.9/82+/-4.1 mm Hg and 90+/-6/49+/-2.4 mm Hg in patients and in control subjects, respectively. During ganglionic blockade, plasma vasopressin concentration increased 24-fold in control subjects and <2-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 8.0+/-2.0 microg in patients and 135+/-35 microg in control subjects before ganglionic blockade and 5.4+/-0.4 microg in patients and 13+/-4.8 microg 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.
Jordan
J
J
Clinical Research Center, Franz Volhard Clinic, Medical Faculty of the Charité, Humboldt-University, Berlin, Germany. jordan@fvk-berlin.de
Toka
H R
HR
Heusser
K
K
Toka
O
O
Shannon
J R
JR
Tank
J
J
Diedrich
A
A
Stabroth
C
C
Stoffels
M
M
Naraghi
R
R
Oelkers
W
W
Schuster
H
H
Schobel
H P
HP
Haller
H
H
Luft
F C
FC
D000293:Adolescent; D000328:Adult; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000002:abnormalities* / Q000098:blood supply / Q000503:physiopathology*; D002531:Cerebellum / Q000098:blood supply; D002536:Cerebral Arteries / Q000002:abnormalities*; D003080:Cold Temperature; D004594:Electrophysiology; D005385:Fingers / Q000002:abnormalities; D005730:Ganglionic Blockers / Q000494:pharmacology; D005799:Genes, Dominant; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D010656:Phenylephrine / Q000494:pharmacology; D011187:Posture; D011311:Pressoreceptors / Q000187:drug effects; D013577:Syndrome; D014636:Valsalva Maneuver; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D005730:Ganglionic Blockers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine