TRPV1 (Transient Receptor Potential Vanilloid 1) Cardiac Spinal Afferents Contribute to Hypertension in Spontaneous Hypertensive Rat

Abstract

Hypertension is associated with increased sympathetic activity. A component of this sympathoexcitation may be driven by increased signaling from sensory endings from the heart to the autonomic control areas in the brain. This pathway mediates the so-called cardiac sympathetic afferent reflex, which is also activated by coronary ischemia or other nociceptive stimuli in the heart. The cardiac sympathetic afferent reflex has been shown to be enhanced in the heart failure state and in renal hypertension. However, little is known about its role in the development or progression of hypertension or the phenotype of the sensory endings involved. To investigate this, we used the selective afferent neurotoxin, resiniferatoxin (RTX) to chronically abolish the cardiac sympathetic afferent reflex in 2 models of hypertension; the spontaneous hypertensive rats (SHRs) and AngII (angiotensin II) infusion (240 ng/kg per min). Blood pressure (BP) was measured in conscious animals for 2 to 8 weeks post-RTX. Epidural application of RTX to the T1-T4 spinal segments prevented the further BP increase in 8-week-old SHR and lowered BP in 16-week-old SHR. RTX did not affect BP in Wistar-Kyoto normotensive rats nor in AngII-infused rats. Epicardial application of RTX (50 µg/mL) in 4-week-old SHR prevented the BP increase whereas this treatment does not lower BP in 16-week-old SHR. When RTX was administered into the L2-L5 spinal segments of 16-week-old SHR, no change in BP was observed. These findings indicate that signaling via thoracic afferent nerve fibers may contribute to the hypertension phenotype in the SHR but not in the Ang II infusion model of hypertension.

Activation of bradykinin-sensitive pericardial afferents increases systemic venous tone in conscious rats

“…Studies employing cardiac afferent ablation in hypertensive animals coupled with measurement of venous tone will be needed to answer this question. Recent work is consistent with this possibility since ablation of cardiac sensory afferents attenuated hypertension development in the SHR (Shanks et al, 2019), a model in which elevation in venous tone and cardiac output are associated with hypertension development.…”

“…Collectively, we believe that these data show that pericardial injection of bradykinin causes systemic venoconstriction sufficient to participate in the overall cardiovascular response to activation of the CSAR. Convincing data show that activity of the CSAR is enhanced in the settings of heart failure (Wang et al, 2017;Wang et al, 2014) and hypertension (Chen et al, 2015;Shanks et al, 2019). Venous tone is increased in heart failure (Nekooeian and Pang, 2000) and in hypertension (Fink and Arthur, 2009;Martin et al, 1998;Fink et al, 2000).…”

The Impact of Insulin Resistance on Cardiovascular Control During Exercise in Diabetes

“…For example, it has been demonstrated recently that desensitization of TPRV1 in cardiac afferent neurons by resiniferatoxin exhibits protective effects against autonomic dysfunction in heart failure animals (124,125). Furthermore, ablation of cardiac afferent nerves by resiniferatoxin at the level of the upper thoracic DRG can prevent the development of hypertension in spontaneously hypertensive rats (126). We previously demonstrated that blockade of TRPV1, which contributes significantly to EPR activation (73), significantly reduced pressor and sympathetic responses to suprastimulation of the metaboreflex (via ischemic hindlimb muscle contraction) in spontaneously hypertensive rats (60).…”

Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Cardiovascular Diseases

“…Previous research has shown that members of the TRP family closely relate to cardiovascular disease ( Ma et al, 2017 ). TRPV1 channel can regulate vascular smooth muscle and improve hypertension, causing heart dysfunction under cold exposure ( Zhang et al, 2012 ; Shanks et al, 2019 ). The TRPV1 and TRPV4 channels are involved in the cardiovascular protection of hypoxia.…”