Effects of age on cardiovascular responses to parathyroid hormone and parathyroid hormone-related protein

In aging rats and humans, blood levels of PTH increase 10- to 20-fold. Since aging is often accompanied by hypertension and abnormal regional blood flows, and since PTH and PTHrP (a polypeptide paracrine substance) have strong cardiac, vasodilator and hypotensive properties, it was determined whether these properties were diminished, or otherwise altered with aging. Three month- (young) and 32-month-old (senescent) F344 x BN rats were used. The rat was anesthetized and a thoracotomy was performed. The heart was removed and perfused in the presence or absence of varying doses of PTH or PTHrP using the Langendorff technique. In addition, segments of thoracic aorta and tail artery were studied for their vasorelaxant responses to the polypeptides. In hearts from both young and senescent rats, both PTH and PTHrP elicited potent dose-dependent increases in coronary blood flow, contractility (dP/dt) and heart rate. Aging resulted in marked alterations in responses to both PTH and PTHrP, including decreased maximum coronary flow, decreased chronotropism and a marked decrease in contractility. Both PTH and PTHrP elicited concentration-related vasorelaxant responses in aorta and tail artery, the responses being substantially greater in aorta. Vasorelaxation was reduced in aorta from senescent animals. No significant age-related differences were observed in the tail artery. In conclusion, the cardiac and vascular effects of PTH and PTHrP were markedly altered with aging. These age-related changes in the PTH and PTHrP actions could contribute to the abnormal regional blood flows and hypertension observed in aging.