Testosterone (TES) and other androgens exert a direct vasorelaxing action on the vasculature in vitro that is structurally specific and independent of cytosolic androgen receptor (AR). The effects of intravenous androgen infusions on mean arterial blood pressure (BP) and heart rate (HR) were determined in conscious, unrestrained, chronically catheterized, ganglionically blocked (hexamethonium, HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR-deficient) rats, 16-20 wk of age. BP and HR were recorded at baseline and with increasing doses of androgens (0.375-6.00 μmol·kg(-1)·min(-1) iv; 10 min/dose). Data are expressed as means ± SE (n = 5-8 rats/group). In SD rats, baseline BP and HR averaged 103 ± 4 mmHg and 353 ± 12 beats/min (bpm). TES produced a dose-dependent reduction in BP to a low of 87 ± 4 mmHg (Δ16%), while HR was unchanged (354 ± 14 bpm). Neither BP (109 ± 3 mmHg) nor HR (395 ± 13 bpm) were altered by vehicle (10% EtOH in 0.9% saline; 0.15 ml·kg(-1)·min(-1), iv). In Tfm, TES produced a similar reduction in BP (99 ± 3 to 86 ± 3 mmHg, Δ13%); HR was unchanged (369 ± 18 bpm). In SD, 5β-dihydrotestosterone (genomically inactive metabolite) produced a greater reduction in BP than TES (102 ± 2 to 79 ± 2 mmHg, Δ23%); HR was unchanged (361 ± 9). A 20-μg iv bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30-40 mmHg, while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC; 20 μg·kg(-1)·min(-1) × 30 min) abolished the hypotensive effects of TES infusion on BP (104 ± 2 vs. 101 ± 2 mmHg) and HR (326 ± 11 vs. 324 ± 8 bpm). These data suggest the systemic hypotensive effect of TES and other androgens involves a direct vasodilatory action on the peripheral vasculature which, like the effect observed in isolated arteries, is structurally specific and AR-independent, and involves activation of nNOS.

A study of 26 patients with truncus arteriosus showed a high prevalence of facial dysmorphism, aortic arch abnormalities, extracardiac malformations, and significant prenatal risk factors. There was little evidence of parathyroid or thymic abnormalities. However, there was laboratory evidence of immune deficiency, especially T-helper lymphocytes, and clinical evidence of predilection to infection. These findings suggest that patients with truncus arteriosus belong to the spectrum of the Di George syndrome.

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The mechanisms underlying the conflicting effects of age and estrogen on cerebrovascular reactivity were examined in the middle cerebral artery (MCA) of mature multigravid (MA) female (F), older reproductively senescent (RS)‐F, and mature male (MM) rats. Ovary‐intact, ovariectomized (OvX) and OvX+estrogen‐replaced (OvX+ER) F were studied. Vasopressin (VP, 10−12–10−7M) reactivity was compared in pressurized MCAs pretreated with indomethacin (Indo, 10μM), NS398 (NS, 10μM), or SC560 (SC, 1μM). In MA‐F, Indo had no effect on VP response, whereas in MM, COX‐1(NS) or COX‐2 (SC) inhibition attenuated maximal reactivity by 25–26%. In contrast, in RS‐F, Indo reduced reactivity by 65%. The effects of oxidative stress on VP reactivity were examined in tempol (TPL, 1mM) treated MCA. In MA‐F, reactivity to VP was 20% lower in OvX+ER than in OvX. TPL reduced reactivity by 40% in OvX but had no effect in OvX+ER. Reactivity to VP in RS‐F was similar in OvX and OvX+ER. TPL attenuated reactivity by 30% in OvX+ER, but had no effect in OvX. These data suggest that: 1) constrictor prostanoids enhance vasoconstrictor responses to VP in MM and in older RS‐F but not in younger MA‐F; 2) estrogen reduces oxidative stress‐induced vasoconstriction in younger MA‐F, but enhances it in older RS‐F. (NIH: HL‐080402)