Cardiac natriuretic peptides: A physiological lineage of cardioprotective hormones?

Vertebrate hearts from fish to mammals secrete peptide hormones with profou nd natriuretic, diuretic, and vasodilatory activity; however, the specific role of these cardiac natriuretic peptides (NPs) in homeostasis is unclear. NPs have been suggested to be involved in salt excretion in saltwater tele osts, whereas they are proposed to be more important in volume regulation i n mammals. In this review, we consider an alternative (or perhaps complemen tary) function of NPs to protect the heart. This hypothesis is based on a n umber of observations. First, evidence for NPs, or NP-like activity has bee n found in all vertebrate hearts thus far examined, from osmoconforming sal twater hagfish to euryhaline freshwater and saltwater teleosts to terrestri al mammals. Thus the presence of cardiac NPs appears to be independent of e nvironmental conditions that may variously affect salt and water balance. S econd, cardiac stretch is a universal, and one of the most powerful, NP sec retagogues. Furthermore, stretch-induced NP release in euryhaline teleosts appears relatively independent of ambient salinity. Third, excessive cardia c stretch that increases end-diastolic volume (EDV) can compromise the mech anical ability of the heart by decreasing actin-myosin interaction (length- tension) or through Laplace effects whereby as EDV increases, the wall tens ion necessary to maintain a constant pressure must also increase. Excessive cardiac stretch can be produced by factors that decrease cardiac emptying (i.e., increased arterial pressure), or by factors that increase cardiac fi lling (i.e., increased blood volume, increased venous tone, or decreased Ve nous compliance). Fourth, the major physiological actions of cardiac NPs en hance cardiac emptying and decrease cardiac filling. In fish, NPs promote c ardiac emptying by decreasing gill vascular resistance, thereby lowering ve ntral aortic pressure. In mammals a similar effect is achieved through pulm onary vasodilation. NPs also decrease cardiac filling by decreasing blood v olume and increasing venous compliance, the latter producing a rapid fall i n central venous pressure. Fifth, the presence of NP clearance receptors in the gill and lung (between the heart and systemic circulation) suggest tha t these tissues may be exposed to considerably higher NP titers than are sy stemic tissues. Thus, a decrease in outflow resistance immediately downstre am from the heart may be the first response to increased cardiac distension . Because the physiology of cardiac NPs is basically the same in fish and m ammals, we propose that the cardioprotective effects of NPs have been well preserved throughout the course of vertebrate evolution. It is also likely that the cardioprotective role of NPs was one of the most primordial homeos tatic activities of these peptides in the earliest vertebrates.