Decreases in Substance P and Vasoactive Intestinal Peptide Concentrations in Plasma of Stroke-Prone Spontaneously Hypertensive Rats.

Mori, Kazuo; Asakura, Shunji; Ogawa, Hiroshi; Sasagawa, Sukenari; Takeyama, Masaharu

doi:10.1536/ihj.34.785

Cited by 9 publications

(5 citation statements)

References 19 publications

(11 reference statements)

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“…We have previously shown the iSP content in the spinal cord is not different between SHR and WKY controls 18 ; however, other investigators have demonstrated reduced circulating levels of this peptide in the SHR and stroke-prone SHR. 8 Therefore, although it is possible to speculate that the decreased activity of SP may contribute to the BP increase in the SHR, this does not appear to be the case in the Dahl-salt rats.…”

Section: Discussionmentioning

confidence: 96%

“…6 Also, reduced levels of SP have been reported in essential hypertension in humans and in stroke-prone SHR. 7,8 Therefore, in these settings both CGRP and SP could contribute to elevated blood pressure through the decreased activity of a potent vasodilator. In contrast, we have reported that CGRP plays a counterregulatory role in deoxycorticosterone acetate (DOCA)-salt hypertension and in subtotal nephrectomy-salt (SN-salt) hypertension.…”

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confidence: 99%

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Role Of Calcitonin Gene-Related Peptide and Substance P in Dahl-Salt Hypertension

2001

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Abstract-Calcitonin gene-related peptide (CGRP) and substance P are known to play a counterregulatory role in acquired models of salt-dependent hypertension. In contrast, neuronal production of these peptides is decreased in the spontaneously hypertensive rat, which may contribute to the elevated blood pressure. To determine the role played by CGRP and substance P in Dahl-salt hypertension, 4-to 6-week-old male salt-resistant (DR) and salt-sensitive (DS) rats were divided into 4 groups (nϭ5/group) and pair-fed low-salt (0.2% NaCl) (DR/LS and DS/LS) and high-salt (8% NaCl) diets (DR/HS and DS/HS) for 3 weeks. After 3 weeks, all the rats had venous (for drug administration) and arterial (for blood pressure monitoring) catheters surgically implanted and were studied in the conscious and unrestrained state. Mean arterial pressure was significantly higher in the DS/HS rats animals (185.8Ϯ1.6 mm Hg, PϽ0.001). Intravenous administration of CGRP and SP receptor antagonists was without effect in any of the groups studied. CGRP and SP mRNA content from dorsal root ganglia were not significantly different between the groups. Whereas immunoreactive CGRP was decreased in the DS groups (DS/HS, 9.4Ϯ0.4 pg/g protein; DS/LS, 11.1Ϯ0.8 pg/g protein; PϽ0.01) compared with the DR groups (DR/HS, 13.9Ϯ0.6 pg/g protein; DR/LS, 14.6Ϯ0.6 pg/g protein), neuronal SP production was similar between all the groups. Thus, CGRP and substance P do not play a counterregulatory role in Dahl-salt hypertension. The decrease in neuronal CGRP expression in DS rats appears to be genetically determined as in SHR, however, and may contribute to the increase in blood pressure following salt-loading. Key Words: rats Ⅲ neuropeptides Ⅲ hypertension, genetic Ⅲ blood pressure Ⅲ RNA Ⅲ radioimmunoassay C alcitonin gene-related peptide (CGRP), a 37 amino acid peptide, is produced by the alternate splicing of the calcitonin/CGRP gene. 1,2 CGRP is the most potent vasodilator discovered to date and has markedly positive chronotropic and inotropic effects. 3 There are 2 CGRP genes, which are called ␣-CGRP and ␤-CGRP in the rat and I and II humans. 3 In the rat and in humans, the 2 peptides differ by 1 amino acid and 3 amino acids, respectively, and their biological activities are similar in most vascular beds. Substance P (SP) is a member of the tachykinin family and, like CGRP, is involved in numerous physiological activities such as neuromodulation, smooth muscle contraction, and vasodilation. 4,5 A prominent site for CGRP and SP synthesis is the dorsal root ganglia (DRG), which contain the cell bodies of sensory neurons that terminate centrally in the spinal cord and peripherally on blood vessels. 3 We have demonstrated that the neuronal expression of CGRP is decreased in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). 6 Also, reduced levels of SP have been reported in essential hypertension in humans and in stroke-prone SHR. 7,8 Therefore, in these settings both CGRP and SP could contribute to elevated blood pressure through the decre...

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Section: Discussionmentioning

confidence: 96%

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confidence: 99%

Role Of Calcitonin Gene-Related Peptide and Substance P in Dahl-Salt Hypertension

2001

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“…Our findings showing an impaired release of substance P in response to activation of renal pelvic sensory receptors in SHR are in analogy with previous studies in hypertensive rats demonstrating a failure of substance P to increase in response to feeding. 28 Likewise, mental stress resulted in a reduced increase in the plasma concentration of substance P in hypertensive compared with normotensive subjects. 29 In addition, several studies show an increased pain threshold in hypertensive men and rats.…”

Section: Discussionmentioning

confidence: 98%

Renal Substance P–Containing Neurons and Substance P Receptors Impaired in Hypertension

et al. 1998

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Abstract-In normotensive rats, increased renal pelvic pressure stimulates the release of prostaglandin E and substance P, which in turn leads to an increase in afferent renal nerve activity (ARNA) and a contralateral natriuresis, a contralateral inhibitory renorenal reflex. In spontaneously hypertensive rats (SHR), increasing renal pelvic pressure failed to increase afferent renal nerve activity. The inhibitory nature of renorenal reflexes indicates that impaired renorenal reflexes could contribute to increased sodium retention in SHR. Phorbol esters, known to activate protein kinase C, increase afferent renal nerve activity in Wistar-Kyoto rats (WKY) but not in SHR. We examined the mechanisms involved in the impaired responses to renal sensory receptor activation in SHR. The phorbol ester 4␤-phorbol 12,13-dibutyrate increased renal pelvic protein kinase C activity similarly in SHR and WKY. Increasing renal pelvic pressure increased afferent renal nerve activity in WKY (27Ϯ2%) but not in SHR. Renal pelvic release of prostaglandin E increased similarly in WKY and SHR, from 0.8Ϯ0.1 to 2.0Ϯ0.4 ng/min and 0.7Ϯ0.1 to 1.4Ϯ0.2 ng/min. Renal pelvic release of substance P was greater (PϽ.01) in WKY, from 16.3Ϯ3.8 to 41.8Ϯ7.4 pg/min, than in SHR, from 9.9Ϯ1.7 to 17.0Ϯ3.2 pg/min. In WKY, renal pelvic administration of substance P at 0.8, 4, and 20 g/mL increased ARNA 382Ϯ69, 750Ϯ233, and 783Ϯ124% ⅐ second (area under the curve of afferent renal nerve activity versus time). In SHR, substance P at 0.8 to 20 g/mL failed to increase ARNA. These findings demonstrate that the impaired afferent renal nerve activity response to increased renal pelvic pressure is related to decreased release of substance P and/or impaired activation of substance P receptors. (Hypertension. 1998;31:815-822.)Key Words: afferent renal nerve activity Ⅲ receptors, sensory Ⅲ prostaglandins Ⅲ protein kinase C Ⅲ substance P Ⅲ rats, inbred SHR O bstruction to urine flow increases renal pelvic pressure and activates renal mechanoreceptors, resulting in an increase in ipsilateral ARNA.1-5 The increase in ARNA produces a fall in contralateral efferent renal sympathetic nerve activity (ER-SNA) and a contralateral diuresis and natriuresis, known as the contralateral inhibitory renorenal reflex. 2Accumulating evidence indicates that the renal nerves contribute to the pathogenesis of hypertension in SHR.6 Peripheral sympathetic nerve activity and, in particular, ERSNA is enhanced in SHR. The nature of the renorenal reflex, that is, a diuresis and natriuresis in association with decreased ERSNA, would suggest that an attenuation of this reflex would result in increased ERSNA leading to water and sodium retention, factors known to contribute to the hypertensive process. 7 Our previous studies in SHR demonstrated that increasing renal pelvic pressure failed to increase ARNA and thus failed to elicit a contralateral renorenal reflex in these rats. 8 The lack of an increase in ARNA in response to increased renal pelvic pressure suggested that the impairment of the reno...

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“…Substance P is also located in sensory nerve endings in blood vessels (Severini et al 2002;Scotland et al 2004) and in the terminals of cardiovascular afferents terminating in the nucleus tractus solitarii, a brainstem nucleus with a pivotal role in the regulation of blood pressure and implicated in baroreceptor regulation (see Helke & Seagard, 2004). Consistent with this are reports that plasma concentrations of substance P are reduced in stroke-prone spontaneously hypertensive rats (Mori et al 1993) and in patients with essential hypertension (Faulhaber et al 1987). Collectively, these findings suggest that a reduction in substance P signalling could contribute to the pathogenesis of these diseases.…”

Section: Introductionmentioning

confidence: 78%

“…Consistent with this are reports that plasma concentrations of substance P are reduced in stroke‐prone spontaneously hypertensive rats (Mori et al . ) and in patients with essential hypertension (Faulhaber et al . ).…”

Section: Introductionmentioning

confidence: 99%

Raised arterial blood pressure in neurokinin‐1 receptor‐deficient mice (NK1R^−/−): evidence for a neural rather than a vascular mechanism

Moyes

Stanford

Hosford

et al. 2016

Experimental Physiology

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New Findings r What is the central question of this study?Does genetic ablation of neurokinin-1 receptors alter arterial blood pressure? r What is the main finding and its importance? NK1R−/− mice have increased mean arterial blood pressure, but without a concomitant change in vascular reactivity. This finding suggests that neurokinin-1 receptors play a role in the neural regulation of blood pressure.Mice with functional ablation of the neurokinin-1 receptor gene, Tacr1, (NK1R −/− ) express behavioural abnormalities equivalent to those seen in attention deficit hyperactivity disorder (ADHD). An established model of ADHD is the spontaneously hypertensive rat, which exhibits high blood pressure owing to increased central sympathetic drive. In light of the evidence that the neurokinin-1 receptor (NK1R) also influences cardiovascular haemodynamics, we have investigated whether NK1R −/− mice exhibit raised blood pressure. Cardiovascular parameters were recorded for 24 h in conscious mice using radiotelemetry. Vascular function was assessed in mesenteric resistance arteries by wire myography. The NK1R −/− mice exhibited a higher blood pressure than wild-type animals throughout the 24 h period. Heart rate and locomotor activity in NK1R −/− mice were higher than in wild-type mice during the night period (active phase), consistent with an ADHD-like phenotype, but not during the day. Mesenteric and renal arteries from NK1R −/− mice exhibited normal vascular function; the responses to vasoconstrictors (U46619 and phenylephrine) and the endothelium-dependent vasodilator, acetylcholine, were not altered in these animals, suggesting that the NK1R does not regulate vascular tone. Analysis of heart rate variability revealed a higher low-frequency to high-frequency ratio in NK1R −/− mice, indicative of increased cardiac sympathetic activity. We propose that the raised blood pressure in NK1R −/− mice could be due to a neural mechanism rather than a change in vascular reactivity. Further studies are required to understand this mechanism and to establish whether a subgroup of ADHD patients with polymorphism of the equivalent (TACR1) gene are affected in a similar way.

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Decreases in Substance P and Vasoactive Intestinal Peptide Concentrations in Plasma of Stroke-Prone Spontaneously Hypertensive Rats.

Cited by 9 publications

References 19 publications

Role Of Calcitonin Gene-Related Peptide and Substance P in Dahl-Salt Hypertension

Role Of Calcitonin Gene-Related Peptide and Substance P in Dahl-Salt Hypertension

Renal Substance P–Containing Neurons and Substance P Receptors Impaired in Hypertension

Raised arterial blood pressure in neurokinin‐1 receptor‐deficient mice (NK1R^−/−): evidence for a neural rather than a vascular mechanism

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Decreases in Substance P and Vasoactive Intestinal Peptide Concentrations in Plasma of Stroke-Prone Spontaneously Hypertensive Rats.

Cited by 9 publications

References 19 publications

Role Of Calcitonin Gene-Related Peptide and Substance P in Dahl-Salt Hypertension

Role Of Calcitonin Gene-Related Peptide and Substance P in Dahl-Salt Hypertension

Renal Substance P–Containing Neurons and Substance P Receptors Impaired in Hypertension

Raised arterial blood pressure in neurokinin‐1 receptor‐deficient mice (NK1R−/−): evidence for a neural rather than a vascular mechanism

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Raised arterial blood pressure in neurokinin‐1 receptor‐deficient mice (NK1R^−/−): evidence for a neural rather than a vascular mechanism