Sympathetic activity and presynaptic adrenoceptor function in patients with longstanding essential hypertension.
OBJECTIVE
To assess the contribution of the sympathetic nervous system to the hypertension in patients with longstanding essential hypertension.


METHODS
Overall sympathetic function, presynaptic adrenoceptors and neuronal re-uptake were examined after withdrawal of medication for at least 3 weeks in eight patients with longstanding essential hypertension and in eight carefully matched normotensive control subjects.


METHODS
Minimal forearm vascular resistance after 10 min ischaemia was used as a measure of structural vascular changes. Overall sympathetic tone was assessed using tilt testing and pressor dose infusion of noradrenaline. The presence and function of presynaptic adrenoceptors and the neuronal re-uptake of noradrenaline were evaluated in the forearm using tracer noradrenaline kinetics with measurement of forearm noradrenaline plasma appearance rate and noradrenaline plasma spillover. Intra-arterial infusions of tritiated noradrenaline, the endogenous alpha- and beta-adrenoceptor agonist adrenaline, the alpha-adrenoceptor blocker phentolamine, the non-adrenergic vasodilator sodium nitroprusside and the neuronal re-uptake inhibitor desipramine were given in the forearm.


RESULTS
We found that the hypertensives had higher minimal forearm vascular resistance, indicating structural vascular changes; decreased overall sympathetic activity, indicated by a lower basal whole-body noradrenaline production rate; enhanced vasopressor sensitivity for exogenously administered noradrenaline with decreased arterial baroreflex sensitivity; indications of decreased forearm neuronal re-uptake; evidence consistent with the presence of presynaptic, release-facilitating beta-adrenoceptors in the forearm, apparently not functionally different between the two groups; and undecisive evidence for the presence of functional presynaptic alpha-adrenoceptors in the forearm.


CONCLUSIONS
In patients with longstanding essential hypertension we found decreased overall sympathetic activity, with indications of decreased forearm neuronal re-uptake, which might have a compensatory role. We found indications of structural vascular changes and diminished baroreflex sensitivity in the hypertensives, which contribute to the hypertension. However, peripheral presynaptic, release-facilitating beta-adrenoceptors seem to be present, which are functionally not clearly different between the two groups. Observations on peripheral presynaptic alpha-adrenoceptors were inconclusive.
Department of Nephrology, University Hospital Leiden, The Netherlands.
P C
PC
Chang
E
E
Kriek
P
P
van Brummelen
D000328:Adult; D000368:Aged; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D005542:Forearm; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011187:Posture; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D017661:Receptors, Presynaptic / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014655:Vascular Resistance / Q000502:physiology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D017661:Receptors, Presynaptic; D009638:Norepinephrine; D004837:Epinephrine