Studies on the Role of the Central and Peripheral Sympathetic Nervous System and the Renin-Aldosterone System on the Onset and Maintenance of High Blood Pressure in Essential Hypertension

These studies were undertaken to clarify the role of the central and peripheral sympathetic nervous system and the renin-aldosterone system on the onset and maintenance of high blood pressure in essential hypertension (EH), and the following examinations were performed; 1) Urinary free norepinephrine and epinephrine excretion (UNEf and UEf), urinary conjugated norepinephrine and epinephrine excretion (UNEconj and UEconj), plasma norepinephrine and epinephrine concentration (PNE and PE), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 52 patients with EH, who were divided into two groups (borderline EH : b-EH, and sustained EH : s-EH), and fifteen normals (N). 2) Cardiac index (CI), total peripheral resistance index (TPRI), appearance time, mean transit time and stroke index (SI) were determined by the dye-dilution method in eight patients with b-EH, ten patients with s-EH and ten N. 3) Clonidine was administered orally in a single dose of 150 μg to seven patients with s-EH and three patients with b-EH, and PNE, PE and growth hormone (GH) were measured before and after the administration. 4) Isoproterenol was infused intravenously in a dose of 0.02 μg/kg/min for 30 min to 18 patients with s-EH and six N, then plasma cyclic AMP (c-AMP) and PRA were determined before, during and after the infusion. 5) Metacholine was injected intramuscularly in a dose of 10 mg to seven N, and PNE, PE and PRA were measured before and after the injection. RESULTS : There were no significant differences of PNE, PE, UNEf and UEf among the three groups (b-EH, s-EH and N), but UNEconj in both b-EH and s-EH was higher than in N (b-EH : p<0.1, s-EH : p<0.05). PRA in s-EH was slightly lower not only in N but also in b-EH. PAC in b-EH and s-EH was slightly lower than in N. The difference of PAC between b-EH and s-EH was not found. CI and SI were higher than in N (p<0.05), but TPRI was normal. In s-EH, TPRI was slightly elevated as compared with b-EH (p<0.1). In s-EH, clonidine caused a significant lowering of both blood pressure and PNE with a simultaneously marked increment of GH; on the other hand, in b-EH blood pressure and PNE did not change significantly in spite of the distinct rise of GH. After the isoproterenol infusion, PRA and c-AMP increased, and there was a significant correlation between the initial level of PRA and the maximal increment of PRA after the infusion in both s-EH and N. Metacholine made PNE, PE and PRA increase in N, the increment of catecholamines was followed by the rise of PRA. These data suggest that the slight hypertonicity of the sympathetic nervous system may be present in both b-EH and s-EH, and that in the early stages of EH, the beta-adrenergic mechanism may be important for the elevation of blood pressure, and in the later stages of EH the alpha-adrenergic mechanism may play a predominant role in the maintenance of high blood pressure. The central noradrenergic system may also be important to the pathogenesis of EH. In some patients with EH, the interaction of the sympathetic nervous system and the renin-aldosterone system may cause high blood pressure, but in the greater part of EH, the renin-aldosterone system plays a smaller part in hypertension.C15