Deficiencies in Cystathionine‐β‐synthase (CBS) lead to hyperhomocysteinemia (HHCy), which is considered a risk factor for cardiovascular, bone and neurological disease. Moreover, CBS is important for the production of cysteine, hydrogen sulfide (H2S) and glutathione. Studying the biological role of CBS in adult mice has been severely hampered by embryological disturbances and perinatal mortality. To overcome these issues and assess the effects of whole‐body CBS deficiency in adult mice, we engineered and characterized a Cre‐inducible Cbs knockout model during ageing. No perinatal mortality occurred before Cbs−/− induction at 10 weeks of age. Mice were followed until 90 weeks of age and ablation of Cbs was confirmed in liver and kidney but not in brain. Severe HHCy was observed in Cbs−/− (289 ± 58 µM) but not in Cbs+/− or control mice (<10 µM). Cbs−/− showed impaired growth, facial alopecia, endothelial dysfunction in absence of increased mortality, and signs of liver or kidney damage. CBS expression in skin localized to sebaceous glands and epidermis, suggesting local effects of Cbs−/− on alopecia. Cbs−/− showed increased markers of oxidative stress and senescence but expression of other H2S producing enzymes (CSE and 3‐MST) was not affected. CBS deficiency severely impaired H2S production capacity in liver, but not in brain or kidney. In summary, Cbs−/− mice presented a mild phenotype without mortality despite severe HHCy. The findings demonstrate that HHCy is not directly linked to development of end organ damage.

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The synthesis, characterization, and pharmacological evaluation of new aryloxyaminopropanol compounds based on substituted (4-hydroxyphenyl)ethanone with alterations in the alkoxymethyl side chain in position 2 and with 2-methoxyphenylpiperazine in the basic part of the molecule are reported. For the in vitro pharmacological evaluation, isolated aorta and atria from normotensive Wistar rats were used. Compared to naftopidil, compounds with ethoxymethyl, propoxymethyl, butoxymethyl, and methoxyethoxymethyl substituent displayed similar α -adrenolytic potency. Compounds with methoxymethyl, ethoxymethyl, and propoxymethyl substituent caused a significant decrease in both spontaneous and isoproterenol-induced beating of isolated rat atria. Naftopidil and the tested substances containing a butoxymethyl and methoxyethoxymethyl substituent had no effect on the spontaneous or isoproterenol-induced beating. The tested substance that had the most pronounced effect was the compound with a propoxymethyl substituent. Its antihypertensive efficacy was investigated in vivo on spontaneously hypertensive rats (SHRs). The systolic blood pressure was found to be significantly lower in SHRs subjected to the treatment for 2 weeks than in untreated SHRs. Naftopidil had no significant effect.