Thermoneutrality induces vascular dysfunction and impaired metabolic function in male Wistar rats: a new model of vascular disease.

OBJECTIVE: Cardiovascular disease is of paramount importance, yet there are few relevant rat models to investigate its pathology and explore potential therapeutics. Housing at thermoneutral temperature (30 °C) is being employed to humanize metabolic derangements in rodents. We hypothesized that housing rats in thermoneutral conditions would potentiate a high-fat diet, resulting in diabetes and dysmetabolism, and deleteriously impact vascular function, in comparison to traditional room temperature housing (22 °C). METHODS: Male Wistar rats were housed at either room temperature or thermoneutral temperatures for 16 weeks on either a low or high-fat diet. Glucose and insulin tolerance tests were conducted at the beginning and end of the study. At the study's conclusion, vasoreactivity and mitochondrial respiration of aorta and carotid were conducted. RESULTS: We observed diminished vasodilation in vessels from thermoneutral rats ( P  < 0.05), whereas high-fat diet had no effect. This effect was also observed in endothelium-denuded aorta in thermoneutral rats ( P  < 0.05). Vasoconstriction was significantly elevated in aorta of thermoneutral rats ( P  < 0.05). Diminished nitric oxide synthase activity and nitrotyrosine, and elevated glutathione activity were observed in aorta from rats housed under thermoneutral conditions, indicating a climate of lower nitric oxide and excess reactive oxygen species in aorta. Thermoneutral rat aorta also demonstrated less mitochondrial respiration with lipid substrates compared with the controls ( P  < 0.05). CONCLUSION: Our data support that thermoneutrality causes dysfunctional vasoreactivity, decreased lipid mitochondrial metabolism, and modified cellular signaling. These are critical observations as thermoneutrality is becoming prevalent for translational research models. This new model of vascular dysfunction may be useful for dissection of targetable aspects of cardiovascular disease and is a novel and necessary model of disease.

Sepiapterin Improves Vascular Reactivity and Insulin-Stimulated Glucose in Wistar Rats.

In the vasculature, sedentary behavior leads to endothelial abnormalities, resulting in elevated cardiovascular disease risk. Endothelial nitric oxide synthase (eNOS) aberrations characterize endothelial dysfunction; eNOS also regulates mitochondrial function. We hypothesized that sepiapterin (a precursor to eNOS cofactor tetrahydrobiopterin (BH4)) supplementation would improve endothelium-dependent vascular relaxation in sedentary animals via modulation of NOS function and mitochondrial activity. Sedentary male Wistar rats were fed ad libitum for a total of 10 weeks. Sepiapterin was administered in diet during the final 5 weeks. Intraperitoneal insulin and glucose tolerance tests (IP-ITT/IP-GTT) were conducted at baseline and endpoint. Aorta was assessed for vasoreactivity and mitochondrial respiration. Insulin tolerance, determined by IP-ITT, significantly improved in rats treated with sepiapterin (p < 0.05, interaction of time and treatment). Acetylcholine- (ACh-) driven vasodilation was significantly greater in aorta from sepiapterin-treated rats as compared with control (76.4% versus 54.9% of phenylephrine contraction at 20 µM ACh, p < 0.05). Sepiapterin treatment resulted in significantly elevated state 3 (9.00 oxygen pmol/sec∗mg versus 8.17 oxygen pmol/sec∗mg, p < 0.05) and 4 (7.28 oxygen pmol/sec∗mg versus 5.86 oxygen pmol/sec∗mg, p < 0.05) aortic mitochondrial respiration with significantly lower respiratory control ratio (p < 0.05) during octanoylcarnitine-driven respiration. Vasodilation and insulin sensitivity were improved through targeting NOS via sepiapterin supplementation.

Chemiotropic behavior of female olive fly (Bactrocera oleae GMEL.) onOlea europaea L.

An interpretation is given of a number of observations on the chemiotropic behavior ofBactrocera oleae in connection with olive maceration water and the fly's return to the olive groves after the first summer rains. To this end, the headspace of both maceration water and leaf leaching water, simulating rainfall, were examined. In both cases, the presence of ammonia, which is generally known to attract fruit flies (Diptera, Tephritidae), was detected and, for the first time, in addition to other compounds that are inert for the fly, the presence of styrene was also detected. This aromatic hydrocarbon was found to be a strong attractant. It is shown that both ammonia and styrene are products of the metabolism of microbial flora present on the olive and leaf surface.

Olea europaea Volatiles attractive and repellent to the olive fruit fly (Dacus oleae, Gmelin).

Comparative study of the headspace (HS) composition from olive leaves, olives of varying degrees of ripeness, and crushed olives revealed significant quantitative and qualitative differences. Three different methods were employed to test the effect of the substances identified on the behavior ofDacus oleae gravid females. Attractive/repellent features were tested by presenting the insects with olfactory choices of a water solution of the test chemicals examined, water (blank), and a highly attractive (control) solution of olive maceration water (MW). Toluene and ethylbenzene, present in leaf and half-ripe olive HIS proved attractive, while (E)-2-hexenal emitted by the crushed olives was found to be decidedly repellent. An oviposition stimulation/deterrence test was carried out on olives placed in proximity to test chemicals under examination in water solution, with olives from the same crop serving as control. In the oviposition testα-pinene, mostly emitted by the leaves and half-ripe olives, emerged clearly as an activant,p-xylene, myrcenone, ethylbenzene,n-octane ando-xylene as weak activants. (E)-2-hexenal and hexanal, both emitted by the crushed olives, displayed an oviposition deterrent effect. The highly repellent property of (E)-2-hexenal was again confirmed in this test.