Sensing of blood pressure increase by transient receptor potential vanilloid 1 receptors on baroreceptors

Abstract

The arterial baroreceptor is critically involved in the autonomic regulation of homoeostasis. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed on both somatic and visceral sensory neurons. Here, we examined the TRPV1 innervation of baroreceptive pathways and its functional significance in the baroreflex. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, was used to ablate TRPV1-expressing afferent neurons and fibers in adult rats. Immunofluorescence labeling revealed that TRPV1 immunoreactivity was present on nerve fibers and terminals in the adventitia of the ascending aorta and aortic arch, the nodose ganglion neurons, and afferent fibers in the solitary tract of the brainstem. RTX treatment eliminated TRPV1 immunoreactivities in the aorta, nodose ganglion, and solitary tract. Renal sympathetic nerve activity, blood pressure, and heart rate were recorded in anesthetized rats. The baroreflex was triggered by lowering and raising blood pressure through intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Inhibition of sympathetic nerve activity and heart rate by the phenylephrine-induced increase in blood pressure was largely impaired in RTX-treated rats. The maximum gain of the baroreflex function was significantly lower in RTX-treated than vehicle-treated rats. Furthermore, blocking of TRPV1 receptors significantly blunted the baroreflex and decreased the maximum gain of baroreflex function in the high blood pressure range. Our findings provide important new information that TRPV1 is expressed along the entire baroreceptive afferent pathway. TRPV1 receptors expressed on baroreceptive nerve endings can function as mechanoreceptors to detect the increase in blood pressure and maintain the homoeostasis.

Fig. 1.

Confocal images show TRPV1-expressing nerve fibers and terminals in the ascending aorta and aortic arch. A–C, TRPV1-immunoreactive nerve fibers and terminals were present in the adventitia of the ascending aorta and aortic arch in vehicle-treated rats. D, TRPV1-immunoreactive nerve fibers were eliminated in the adventitia of the ascending aorta of in one RTX-treated rat. Maximum projection images were obtained from the Z-stack confocal images.

Fig. 2.

Confocal images show the spatial relationship between TRPV1- and NF200-immunoreactive nerve fibers in the ascending aorta and aortic arch. A, TRPV1- and NF200-immunoreactive nerve fibers and terminals were present in the adventitia of the ascending aorta and aortic arch of one vehicle-treated rat. Colocalization of TRPV1 and NF200 immunoreactivities is indicated in yellow when two images are digitally merged. B, nerve fibers immunoreactive to both TRPV1 and NF200 were eliminated in the ascending aorta of one RTX-treated rat. Maximum projection images were obtained from the Z-stack confocal images.

Fig. 3.

Confocal images depict the presence of TRPV1- and IB₄-positive neurons in the NG and DRG. A, TRPV1- and IB₄-positive neurons in the NG of one vehicle- and one RTX-treated rat. TRPV1 and IB₄ are present in the majority of NG neurons. RTX treatment eliminated all TRPV1-immunoreactive neurons and most IB₄-positive neurons in the NG. B, TRPV1- and IB₄-positive neurons in the DRG of one vehicle- and one RTX-treated rat. RTX treatment eliminated all TRPV1-expressing neurons and most IB₄-positive neurons in the DRG. All images are single confocal optical sections.

Fig. 4.

Confocal images show the presence of TRPV1- and IB₄-positive afferent fibers in the solitary tract. A, low- and high-magnification confocal images show the presence of TRPV1- and IB₄-positive afferent fibers in the solitary tract (ST) in a vehicle-treated rat. The majority of TRPV1-immunoreactive fibers are colocalized with IB₄ in the ST and terminate in the medial region of the nucleus tractus solitarius (mNTS). B, low- and high-magnification confocal images show diminished TRPV1- and IB₄-positive nerve fibers in the ST of one RTX-treated rat. All images are single confocal optical sections.

Fig. 5.

Baroreflex functions in vehicle- and RTX-treated rats. A and B, original recordings depict the changes in RSNA and HR in response to ABP changes induced by intravenous injection of PE in one vehicle- and one RTX-treated rat. C and D, baroreflex function curves derived from reflex changes in RSNA and HR in 15 vehicle- and 12 RTX-treated rats. Inset, gain of the mean baroreflex curves. The maximum gain values in C in vehicle- and RTX-treated rats are −1.8 ± 0.3 and −1.1 ± 0.2%·mm Hg⁻¹ (P < 0.05), respectively. The maximum gain values in D in vehicle- and RTX-treated rats are −1.2 ± 0.1 and −0.8 ± 0.2 bpm·mm Hg⁻¹ (P < 0.05), respectively. Int-RSNA, integrated RSNA.

Fig. 6.

Iodo-RTX blocks capsaicin-induced changes in the blood pressure, RSNA, and HR. A, original records show the effect of capsaicin (10 μg/kg i.v.) on ABP, RSNA, and HR in one rat. B, effect of capsaicin (10 μg/kg i.v.) on ABP, RSNA, and HR was diminished after pretreatment with iodo-RTX (1 μmol/kg i.v.) in one rat. C, group data show the effect of capsaicin (10 μg/kg i.v.) on changes in MAP, RSNA, and HR in rats pretreated with the vehicle (n = 6) or iodo-RTX (n = 8). *, P < 0.05 compared with the respective control. Int-RSNA, integrated RSNA.

Fig. 7.

Effect of blocking TRPV1 on the baroreflex function. A and B, original recordings show reflex changes in RSNA and HR in response to ABP increases induced by injection of PE in one vehicle- and one iodo-RTX (1 μmol/kg i.v.)-treated rat. C and D, baroreflex function curves derived from reflex changes in RSNA and HR in six vehicle- and seven iodo-RTX-treated rats. Inset, gain of the mean baroreflex curves. The maximum gain values in C in vehicle- and iodo-RTX-treated rats are −1.7 ± 0.3 and −1.1 ± 0.2% · mm Hg⁻¹ (P < 0.05), respectively. The maximum gain values in D in vehicle- and iodo-RTX-treated rats are −1.2 ± 0.2 and −0.7 ± 0.1 bpm·mm Hg⁻¹ (P < 0.05), respectively. Int-RSNA, integrated RSNA.