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Respiration and blood pressure (BP) are regulated to maintain optimal delivery of O2 to every cell in the body. Arterial hypoxemia is sensed by the carotid body (CB), which initiates sympathetic reflex arcs to the diaphragm to increase ventilation, and to the adrenal medulla (AM) to increase catecholamine secretion and thereby increase BP. However, the underlying molecular mechanisms have not been fully delineated. Here, we report that the relative activities of hypoxia-inducible factor-1 (HIF-1) and HIF-2 determine the set point for the CB and AM, with respect to their maintenance of BP and respiration. In Hif2a+/- mice, which are heterozygous for a knockout allele at the locus encoding HIF-2α, expression of HIF-1α and NADPH oxidase 2 was increased in the CB and AM, resulting in an oxidized intracellular redox state with augmented sensitivity to hypoxia, increased BP, and respiratory abnormalities, which were all normalized by treatment with a HIF-1α inhibitor or a superoxide anion scavenger. By contrast, in Hif1a+/- mice, which are heterozygous for a knockout allele at the locus encoding HIF-1α, the expression of HIF-2α and superoxide dismutase 2 was increased in the CB and AM, resulting in a reduced intracellular redox state with impaired CB and ventilatory responses to chronic hypoxia, which were normalized by treatment with a HIF-2α inhibitor. None of the abnormalities that were observed in Hif1a+/- or Hif2a+/- mice were observed in Hif1a+/-; Hif2a+/- double- heterozygous mice. Our results demonstrate that redox balance in the CB and AM, which is determined by mutual antagonism between HIF-α isoforms, establishes the set point for responses of the CB and AM to hypoxia, and is required for the maintenance of normal BP and respiration.

Santalum album L. (Sandalwood) is one of the pharmacologically valued tree species. The essential oil derived from its heartwood has much more commercial importance, and is an active ingredient in various traditional medicine systems for the management and prevention of various illnesses all over the world. The versatile therapeutic and healthcare importance of Sandalwood is attributed to the rich source of phytochemicals, particularly sesquiterpenes. A variety of biological properties and impending health benefits of Sandalwood have been testified, including anti-microbial, anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic activities, and protecting properties on the gastric mucosa, liver and nervous system. No significant toxicity has been indicated by Sandalwood oil or its individual constituents. The present chapter discusses traditional uses, phytochemistry and pharmacological activities of Sandalwood. Also, it provides an understanding of Sandalwood oil extraction methods, chemistry of the compounds and their medicinal importance.