Cardiovascular Effects of Octreotide, a Long‐Acting Somatostatin Analog

Somatostatin, first isolated from ovine hypothalami by Guillemin’s group at the Salk Institute in 1973 (4), is a tetradecapeptide that inhibits growth hormone (GH) release from the pituitary gland (Fig. 1). Large amounts of somatostatin are found in many human tissues, including the D cells of the stomach, intestine, and pancreatic islets; the central nervous system; and the neurons and fibers of both the submucosal and the myenteric plexuses (23,44). In addition to the GH-inhibiting effect, somatostatin suppresses the release of insulin-like growth factor-1 (IGF-1), serotonin, vasoactive intestinal polypeptide, gastrin, insulin, glucagon, secretin, motilin, and pancreatic polypeptides (Table 1). Somatostatin also exerts an extraordinary range of physiological effects on the gastrointestinal tract, such as modifying intestinal transit time, regulating intestinal water and electrolyte transport, reducing splanchnic blood flow, and inhibiting pancreatic exocrine function. These effects suggest that somatostatin might have a broad therapeutic potential, but its clinical application has been limited by its extremely short plasma half-life of 1 to 3 min (54). Octreotide is a synthetic cyclic octapeptide that is homologous with the natural hormone somatostatin at the 4 amino acid sequence (phenylalanine [Phe]–tryptophan [Trp]– lysine [Lys]–threonine [Thr]) within the ring structure that confers biological activity (Fig. 1) (3). Degradation has been slowed by the substitution of L-amino acids with theDstereoisomers at the first ( D-Phe) and fourth ( D-Trp) positions. The resulting half-life has been reported to be 80 times that of somatostatin (29). Because of its prolonged half-life, octreotide is free from rebound hypersecretion of hormones after it is discontinued (30). Octreotide is now widely accepted as a therapeutic agent for reducing the blood GH and IGF-1 levels in acromegalic patients and as a control for the symptoms of patients with neuroendocrine tumors of the gut.