Portal Osmopressor Mechanism Linked to Transient Receptor Potential Vanilloid 4 and Blood Pressure Control

Abstract

Abstract-Human subjects with impaired baroreflex function cannot buffer rises or falls in blood pressure (BP), thus allowing BP effects of endogenous or environmental stimuli that previously escaped detection to emerge dramatically. Studies in these patients led us to discover that water ingestion induced a robust increase in BP and vascular resistance. Here, using a mouse model of baroreflex impairment, we show that the increase in blood pressure after water ingestion is mediated through sympathetic nervous system activation and that the osmosensitive transient receptor potential vanilloid 4 channel (Trpv4) is an essential component of the response. Although portal osmolality decreases after water ingestion in both wild-type and Trpv4 Ϫ/Ϫ mice, only the wild-type animals show a pressor response. The same volume of physiological saline does not elicit an increase in BP, suggesting osmolality as the stimulus. The osmopressor response to water, and Trpv4 thus represent new factors now implicated in the physiology of BP regulation. (Hypertension. 2010;55:1438-1443.) Key Words: Trpv4 Ⅲ blood pressure Ⅲ osmopressor Ⅲ sympathetic nervous system Ⅲ baroreflex S tudies in patients with baroreflex impairment led us to discover that water ingestion increases blood pressure (BP) and vascular resistance. We found that ingestion of 16 oz (473 mL) of water induces a profound increase in systolic BP, averaging Ϸ40 mm Hg, with occasional increases Ͼ75 mm Hg. The effect appears within 10 minutes, is maximal at 25 to 40 minutes, and largely dissipates by 90 minutes after ingestion. Although the effect of water was greatest in individuals with impaired baroreflex buffering, it was also present in healthy persons. In healthy young subjects with intact baroreflexes, water elicits an increase in peripheral vascular resistance without an increase in BP because of a compensatory reduction in cardiac output. 1 Importantly, water ingestion raises plasma norepinephrine but not renin or vasopressin, supporting a sympathetic nervous system mechanism. 2,3 Furthermore, induction of reversible autonomic blockade with the autonomic ganglionic blocking drug trimethaphan abolishes the pressor action of water. 2 Although these studies in human subjects suggest a sympathetic nervous system mechanism for the pressor action of water, we sought to discover the physiological and molecular basis of the response. There has been increasing interest in splanchnic, neural, and vascular mechanisms in BP control in a number of animal models. 4 The transient receptor potential cation channel family, especially the vanilloid family (TRPV), constitutes potential mediators of the pressor response to water. These channels mediate the effects of many environmental factors, including osmolality and stretch, on neuronal and cardiovascular function. 5 Trpv4, in particular, is sensitive to osmotic perturbations 6,7 and is found along the gastrointestinal (GI) tract, mesenteric vessels, liver, cholangiocytes, dorsal root ganglia, and other locations throughout the body. ...

Comparative effects of glucose and water drinks on blood pressure and cardiac function in older subjects with and without postprandial hypotension

“…This concept is supported strongly by the outcome of studies in animals (McHugh et al. 2010). Gastric distension induced by a balloon increases muscle sympathetic nerve activity, the so‐called “gastrovascular reflex,” a response known to be attenuated in the healthy elderly (van Orshoven et al.…”

Hypertonicity Sensing in Organum Vasculosum Lamina Terminalis Neurons: A Mechanical Process InvolvingTRPV1But NotTRPV4

“…The information encoded by the electrical activity of these neurons is then relayed synaptically to diverse subsets of homeostatic effector neurons that induce appropriate osmoregulatory responses such as thirst, natriuresis, and antidiuretic hormone release (Denton et al, 1996;McKinley et al, 2006;Johnson, 2007;Bourque, 2008;Hollis et al, 2008). Interestingly, peripheral osmoreceptors located in the hepatoportal area are capable of detecting postingestion salt and water loads and modulating central osmoregulatory responses (Baertschi and Vallet, 1981;Choi-Kwon and Baertschi, 1991;McHugh et al, 2010;Lechner et al, 2011). It is presently unclear whether these peripheral receptors communicate independently with central effector neurons or if they modulate OVLT neurons via synaptic inputs (Bourque, 2008).…”

“…However the conclusion that Trpv1 encodes an osmore-ceptor channel was recently challenged because hypertonicityinduced expression of the immediate early gene Fos is maintained in the OVLT of mice lacking the gene (Taylor et al, 2008). Moreover, previous studies have indicated that another member of the TRPV gene family, Trpv4, is strongly expressed in the OVLT (Liedtke et al, 2000), and deletion of Trpv4 in mice attenuates Fos expression and osmoregulatory responses in vivo (Liedtke and Friedman, 2003;McHugh et al, 2010;Lechner et al, 2011). In this study we therefore examined the cellular basis for hypertonicity sensing in mouse OVLT neurons and determined whether this process requires expression of both Trpv1 and Trpv4.…”

Acute effect of oral water intake during exercise on post-exercise hypotension

“…Studies in mice suggest that this osmopressor response may involve activation of transient receptor potential vanilloid 4 receptors, which may be located on putative peripheral osmoreceptors in the portal vein and liver. 33,34 However, the afferent nerve cell population serving as peripheral osmosensors and the exact transduction mechanisms are still not well understood. It should be emphasized that this osmopressor response is not induced by saline infusion and/or liquid containing the sodium chloride.…”