Studies of the mechanisms underlying impairment of beta-adrenoceptor-mediated effects in human hypertension.
To investigate the impairment of beta-adrenoceptor responsiveness in human hypertension, we evaluated the effect of an oral salt load (400 mEq/day of NaCl for 7 days) on plasma catecholamine concentrations and beta-adrenoceptor-mediated effects in 11 young patients with mild essential hypertension. Responses of heart rate and plasma cAMP to isoproterenol administration were used as indices of beta-adrenoceptor responsiveness. Salt loading induced a significant reduction in the dose of isoproterenol required to raise the heart rate by 25 bpm (CD25) (from 7.6 +/- 1.5 to 5.3 +/- 0.9 micrograms, p less than 0.05) and an increase in the slopes of the regression lines for heart rate changes and isoproterenol doses (delta HR/IS) (from 3.3 +/- 0.6 to 4.7 +/- 0.7, p less than 0.05) and for plasma cyclic AMP (cAMP) level changes and isoproterenol doses (delta cAMP/IS) (from 0.3 +/- 0.06 to 1.4 +/- 0.3, p less than 0.05). After salt loading there was a significant reduction in plasma catecholamine concentrations with a significant relationship between changes in upright plasma epinephrine levels and changes in CD25 (r = 0.904, p less than 0.01) and in the slopes for delta HR/IS (r = 0.983, p less than 0.001) and delta cAMP/IS (r = 0.922, p less than 0.001). These results support the hypothesis that the impairment of beta-adrenoceptor sensitivity observed in human hypertension is associated with a beta-adrenoceptor overstimulation due to chronically elevated adrenergic tone.
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D012965:Sodium Chloride; D000450:Aldosterone; D000242:Cyclic AMP; D012083:Renin; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine