The Arg16 polymorphism of the beta2-adrenergic receptor is associated with enhanced agonist-mediated desensitization in the vasculature, and the Glu27 polymorphism is associated with increased agonist-mediated responsiveness. Therefore, polymorphisms of the beta2-adrenergic receptor are potentially important determinants of the vascular response to stress.

There is reduced sensitivity of Gly389 homozygotes to a beta-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to beta-blockade.

There are marked interethnic differences in beta 1-adrenoceptor-mediated responsiveness, with sensitivity decreased in African-Americans and increased in Chinese compared with Caucasians. Therefore, the frequency of a common naturally occurring polymorphism of the human beta 1-adrenoceptor gene (Arg389Gly), which has functional importance in vitro, was determined in 194 African-Americans, 316 Caucasian-Americans, 221 Hispanic-Americans and 142 Chinese. African-Americans were found to have a significantly lower frequency of the Arg389 allele than the other three ethnic groups (all P < 0.01). In the populations studied, the order of the distribution of the Arg389 allele was: Chinese (74%) > Caucasians (72%) > Hispanics (67%) > African-Americans (58%). To determine the functional significance of the Arg389Gly beta 1-adrenoceptor polymorphism, in-vivo heart rate responses to exercise were compared in healthy subjects homozygous for the Arg (n = 9) and Gly (n = 8) alleles. Heart rate response to exercise was not affected by genotype (P = 0.4). Although ethnic differences in the frequency of the beta 1-adrenoceptor Arg389Gly polymorphism exist, the polymorphism does not appear to have functional significance in healthy subjects and therefore may not contribute to ethnic differences in response to drugs acting through the beta 1-adrenoceptor.

In healthy men sildenafil increased sensitivity to nitroglycerin, an exogenous NO donor, approximately 4-fold but did not affect endothelium-dependent, NO-mediated responses in either the hand vein or forearm vasculature. Differential vascular responses to sildenafil may localize its enhancement of endogenous NO-mediated vasodilation to vascular beds such as the corpus cavernosum.

Aims Chloroquine treatment of malaria fever, results in a generalized pruritus of unknown mechanism in up to 60% of adult Africans, by contrast pruritus is unusual in Caucasians following chloroquine use. Methods We conducted a double-blind, randomized, parallel group study to examine and compare the antipruritic effects of promethazine, niacin, prednisolone and their combination on pruritus induced by chloroquine, in 28 historical itching patients with parasitologically proven malaria fever. We also evaluated the role of the antecedent malaria parasite density in the severity of chloroquine pruritus intensity. Results The concurrent administration of chloroquine (2.1g base total dose) with prednisolone caused a statistically significant reduction in the pruritus AUC (0, 72 h) (P<0.001 ANOVA) compared with the antihistamine promethazine alone. The areas under the pruritus intensity-time curve were promethazine 105±28 (units h), niacin 76±22, prednisolone 28±24, and prednisolone and niacin 34±17 ( P<0.001 ANOVA). The 95% confidence interval for the difference in the pruritus AUC between prednisolone and promethazine was 8.4 to 145.6 units h. There was a statistically significant and positive correlation between the pruritus intensity (AUC 0, 72 h) and the malaria parasite load in the itching subjects, not receiving prednisolone (n=9) (r=0.73, P=0.026 ANOVA). Conclusion A single oral dose of prednisolone (10 mg) may be preferable to the antihistamine promethazine (25 mg ) as an antipruritic agent for concurrent prescription with chloroquine in individuals predisposed to severe itching. Malaria parasite clearance and clinical amelioration were unaffected by any of the treatments.