Abstract
Patients with essential hypertension show an increase in vascular resistance. It is unclear whether this is caused by structural changes in the arterial wall or by hyperresponsiveness of vascular smooth muscle to endogenous alpha adrenergic agonists. Using the dorsal hand vein compliance technique we compared the changes in diameter of superficial veins in response to phenylephrine, an alpha 1 adrenergic receptor agonist, and to nitroglycerin, a venorelaxant, in patients with essential hypertension and in normotensive subjects. The dose of phenylephrine that produced 50% of maximal venoconstriction (ED50) in the hypertensive subjects was 257 ng/min (geometric mean; log mean +/- SD was 2.41 +/- 0.54). In the control subjects the ED50 was 269 ng/min (geometric mean; log mean was 2.43 +/- 0.43). Maximal response (Emax) for phenylephrine was 84 +/- 13% in the hypertensive subjects and 90 +/- 6% in the control subjects. Differences in the group means of the ED50 (P = 0.92) or the Emax (P = 0.27) were not significant. There were no significant differences in the ED50 (P = 0.54) or the Emax (P = 0.08) for nitroglycerin between the two groups. These results show no evidence for a generalized change in alpha adrenergic responsiveness in hypertension and support the concept that increased blood pressure responses to alpha adrenergic stimulation in hypertensives are due to structural and geometric changes in the arterial wall rather than to an increased responsiveness of postsynaptic alpha adrenergic receptors. The phenylephrine studies were repeated in seven hypertensive patients during treatment with prazosin, an alpha 1 adrenergic antagonist. The mean dose ratio of the shift in phenylephrine ED50 (ED50 during prazosin therapy/ED50 before prazosin therapy) was 6.1. This indicates that small doses of prazosin (1-2 mg) cause significant in vivo shifts in the dose-response relationship of alpha adrenergic agonists. The dorsal hand vein compliance technique is useful in detecting systemic effects of alpha adrenergic antagonists.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aellig W. H. A new technique for recording compliance of human hand veins. Br J Clin Pharmacol. 1981 Mar;11(3):237–243. doi: 10.1111/j.1365-2125.1981.tb00527.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alradi A. O., Carruthers S. G. Evaluation and application of the linear variable differential transformer technique for the assessment of human dorsal hand vein alpha-receptor activity. Clin Pharmacol Ther. 1985 Nov;38(5):495–502. doi: 10.1038/clpt.1985.214. [DOI] [PubMed] [Google Scholar]
- Bülbring E., Tomita T. Catecholamine action on smooth muscle. Pharmacol Rev. 1987 Mar;39(1):49–96. [PubMed] [Google Scholar]
- De Mey J., Vanhoutte P. M. Uneven distribution of postjunctional alpha 1-and alpha 2-like adrenoceptors in canine arterial and venous smooth muscle. Circ Res. 1981 Jun;48(6 Pt 1):875–884. doi: 10.1161/01.res.48.6.875. [DOI] [PubMed] [Google Scholar]
- Egan B., Panis R., Hinderliter A., Schork N., Julius S. Mechanism of increased alpha adrenergic vasoconstriction in human essential hypertension. J Clin Invest. 1987 Sep;80(3):812–817. doi: 10.1172/JCI113138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eichler H. G., Hiremath A., Katzir D., Blaschke T. F., Hoffman B. B. Absence of age-related changes in venous responsiveness to nitroglycerin in vivo in humans. Clin Pharmacol Ther. 1987 Nov;42(5):521–524. doi: 10.1038/clpt.1987.191. [DOI] [PubMed] [Google Scholar]
- Elliott H. L., Sumner D. J., McLean K., Reid J. L. Effect of age on the responsiveness of vascular alpha-adrenoceptors in man. J Cardiovasc Pharmacol. 1982 May-Jun;4(3):388–392. doi: 10.1097/00005344-198205000-00008. [DOI] [PubMed] [Google Scholar]
- Folkow B. Physiological aspects of primary hypertension. Physiol Rev. 1982 Apr;62(2):347–504. doi: 10.1152/physrev.1982.62.2.347. [DOI] [PubMed] [Google Scholar]
- Folkow B. The fourth Volhard lecture: cardiovascular structural adaptation; its role in the initiation and maintenance of primary hypertension. Clin Sci Mol Med Suppl. 1978 Dec;4:3s–22s. doi: 10.1042/cs055003s. [DOI] [PubMed] [Google Scholar]
- Goldstein D. S. Arterial baroreflex sensitivity, plasma catecholamines, and pressor responsiveness in essential hypertension. Circulation. 1983 Aug;68(2):234–240. doi: 10.1161/01.cir.68.2.234. [DOI] [PubMed] [Google Scholar]
- Grimm M., Weidmann P., Keusch G., Meier A., Glück Z. Norepinephrine clearance and pressor effect in normal and hypertensive man. Klin Wochenschr. 1980 Nov 3;58(21):1175–1181. doi: 10.1007/BF01478873. [DOI] [PubMed] [Google Scholar]
- Hoffman B. B., Michel T., Kilpatrick D. M., Lefkowitz R. J., Tolbert M. E., Gilman H., Fain J. N. Agonist versus antagonist binding to alpha-adrenergic receptors. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4569–4573. doi: 10.1073/pnas.77.8.4569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoffman B. B. Regulation of alpha and beta adrenergic receptors in man. Clin Endocrinol Metab. 1983 Mar;12(1):1–13. doi: 10.1016/s0300-595x(83)80026-7. [DOI] [PubMed] [Google Scholar]
- Hollister A. S., Onrot J., Lonce S., Nadeau J. H., Robertson D. Plasma catecholamine modulation of alpha 2 adrenoreceptor agonist affinity and sensitivity in normotensive and hypertensive human platelets. J Clin Invest. 1986 May;77(5):1416–1421. doi: 10.1172/JCI112452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martin S. A., Alexieva S., Carruthers S. G. The influence of age on dorsal hand vein responsiveness to norepinephrine. Clin Pharmacol Ther. 1986 Sep;40(3):257–260. doi: 10.1038/clpt.1986.172. [DOI] [PubMed] [Google Scholar]
- Pan H. Y., Hoffman B. B., Pershe R. A., Blaschke T. F. Decline in beta adrenergic receptor-mediated vascular relaxation with aging in man. J Pharmacol Exp Ther. 1986 Dec;239(3):802–807. [PubMed] [Google Scholar]
- Seideman P., Grahnén A., Haglund K., Lindström B., von Bahr C. Prazosin dynamics in hypertension: relationship to plasma concentration. Clin Pharmacol Ther. 1981 Oct;30(4):447–454. doi: 10.1038/clpt.1981.187. [DOI] [PubMed] [Google Scholar]
- Vanhoutte P. M., Shepherd J. T. Adrenergic pharmacology of human and canine peripheral veins. Fed Proc. 1985 Feb;44(2):337–340. [PubMed] [Google Scholar]
- Vlachakis N. D. Blood pressure response to norepinephrine infusion in relationship to plasma catecholamines and renin activity in man. J Clin Pharmacol. 1979 Oct;19(10):654–661. doi: 10.1002/j.1552-4604.1979.tb01628.x. [DOI] [PubMed] [Google Scholar]