Comparison of somatosympathetic reflex in normotensive and spontaneously hypertensive rats

In chloralose anaesthetized and paralyzed normotensive (Wistar, Wistar--Kyoto) and spontaneously hypertensive rats (SHR), a somatosympathetic reflex in the cervical sympathetic trunk elicited by a single electrical shock to forelimb afferent fibres in the median nerve was recorded. It has been shown that the elicited response of SHR is similar to the response of normotensive rats. Amplitude of somatosympathetic reflex in SHR is larger than that of somatosympathetic reflex in normotensive animals. It is supposed that somatosympathetic reflex in hypertensive and normotensive rats is formed in the same way. However, reflex excitability of sympathetic nervous system in SHR is greater.     

Study of tonic and evoked electrical activity in efferent fibers of the sympathetic nerve in white rats

In anaesthetised Wistar rats, electrical sympathetic activity and a somatosympathetic reflex in the cervical sympathetic trunk elicited by a single electrical shock to forelimb or hindlimb afferent nerves, were recorded. The spontaneous activity was shown to conform with the pulse and respiratory waves of arterial pressure. Somatosympathetic reflex consists of early and late discharges evoked by somatic myelinated afferent fibres stimulation, and C-response elicited by stimulation of unmyelinated afferent fibres in spinal nerves.     

Neuromedin U causes biphasic cardiovascular effects and impairs baroreflex function in rostral ventrolateral medulla of spontaneously hypertensive rat

Neuromedin U (NMU) causes biphasic cardiovascular and sympathetic responses and attenuates adaptive reflexes in the rostral ventrolateral medulla (RVLM) and spinal cord in normotensive animal. However, the role of NMU in the pathogenesis of hypertension is unknown. The effect of NMU on baseline cardiorespiratory variables in the RVLM and spinal cord were investigated in urethane-anaesthetized, vagotomized and artificially ventilated male spontaneously hypertensive rats (SHR) and Wistar–Kyoto rats (WKY). Experiments were also conducted to determine the effects of NMU on somatosympathetic and baroreceptor reflexes in the RVLM of SHR and WKY. NMU injected into the RVLM and spinal cord elicited biphasic response, a brief pressor and sympathoexcitatory response followed by a prolonged depressor and sympathoinhibitory response in both hypertensive and normotensive rat models. The pressor, sympathoexcitatory and sympathoinhibitory responses evoked by NMU were exaggerated in SHR. Phrenic nerve amplitude was also increased following intrathecal or microinjection of NMU into the RVLM of both strains. NMU injection into the RVLM attenuated the somatosympathetic reflex in both SHR and WKY. Baroreflex sensitivity was impaired in SHR at baseline and further impaired following NMU injection into the RVLM. NMU did not affect baroreflex activity in WKY. The present study provides functional evidence that NMU can have an important effect on the cardiovascular and reflex responses that are integrated in the RVLM and spinal cord. A role for NMU in the development and maintenance of essential hypertension remains to be determined.     

The relationship between altered blood vessel structure, hypertension, and the sympathetic nervous system

The relationship between sympathetic innervation and arterial medial development has been examined in normotensive, hypertensive, and diabetic rats. Using the jejunal artery as a model, the number of nerve fibres innervating the artery as determined from fluorescent preparations, and the medial thickness and lumen diameter as measured from resin embedded specimens were correlated from animals prepared in various ways. The rats used were normal Sprague-Dawley (SD), SD with induced hypertension, SD with diabetes induced with streptozotocin, SD sympathectomized with 6-hydroxydopamine, spontaneously hypertensive rats (SHR), SHR treated with capsaicin to prevent hypertension development, Wistar Kyoto rats (WKY), and WKY treated with capsaicin. Examination of the jejunal arteries from these rats at 12 weeks of age following normal development, or 8 weeks of hypertension development, or 8 and 12 weeks of diabetes, showed that increased innervation occurred in the SHR under all conditions, and in the diabetic rats after 8 weeks of diabetes. Medial hypertrophy occurred in the SHR and in the SD hypertensive only. It is concluded that the special relationship which exists between the sympathetic innervation and arterial media in the SHR does not occur during hypertension development in the SD rat, nor is it necessary for normal medial development in the SD rat. The sympathetic innervation does appear to have a trophic influence on vascular smooth muscle of diabetic rats, at least in the early stages of the disease.     

Exaggerated natriuresis in experimental hypertension

The exaggerated natriuretic response to intravenous isotonic saline volume expansion in conscious spontaneous hypertensive rats (SHR), compared to normotensive Wistar-Kyoto rats (WKY), is associated with an exaggerated inhibition of renal nerve activity. Following bilateral renal denervation, the natriuresis was significantly attenuated in SHR but unaffected in WKY. Thus, the exaggerated natriuretic response to intravenous isotonic saline in SHR is dependent on their enhanced inhibition of renal nerve activity. Conscious Dahl salt-sensitive rats, on either low or high salt diet, did not exhibit an exaggerated natriuretic response to intravenous isotonic saline volume expansion which may be explained by their known impairment of cardiopulmonary baroreceptor reflex mediated suppression of efferent sympathetic nerve activity during intravenous volume expansion. Conscious hypertensive DOCA-NaCl rats exhibited an exaggerated natriuretic response to oral but not to intravenous isotonic saline volume expansion, suggesting differences in gastrointestinal absorption of isotonic saline. It is concluded that enhanced inhibition of efferent renal sympathetic nerve activity via cardiopulmonary baroreceptor reflex activation contributes to the exaggerated natriuretic response to intravenous isotonic saline volume expansion in certain models of experimental hypertension.     

Semiquantitative histochemical investigation of lysosomal enzyme activities in the aortic endothelial cells of rats with renal hypertension

To obtain information about changes in lysosomal enzyme activities in the aortic endothelial cells in arterial hypertension, semi-quantitative histochemical investigations of acid phosphatase (Ac-Pase) and N-acetyl-beta-glucosaminidase (NAGase) activities in the aorta of rats with renal hypertension were performed on "H?utchen" monolayer preparations. The aortic endothelial cells in renal hypertensive animals showed increased Ac-Pase and NAGase activities compared with those in control normotensive rats and tended to increase with advancing age. These results, like our previous data from spontaneously hypertensive rats (SHR), indicated that degeneration of endothelial cells, expressed by increased lysosomal enzyme activity, was accelerated by hypertension, and the possible participation of genetic factors in the activation of these enzymes in SHR was ruled out. Increased lysosomal enzyme activity may be involved in the development of other hypertensive vascular changes.     

Sympathetic activation increases basilar arterial blood flow in normotensive but not hypertensive rats

The close apposition between sympathetic and parasympathetic nerve terminals in the adventitia of cerebral arteries provides morphological evidence that sympathetic nerve activation causes parasympathetic nitrergic vasodilation via a sympathetic-parasympathetic interaction mechanism. The decreased parasympathetic nerve terminals in basilar arteries (BA) of spontaneously hypertensive rat (SHR) and renovascular hypertensive rats (RHR) compared with Wistar-Kyoto rats (WKY), therefore, would diminish this axo-axonal interaction-mediated neurogenic vasodilation in hypertension. Increased basilar arterial blood flow (BABF) via axo-axonal interaction during sympathetic activation was, therefore, examined in anesthetized rats by laser-Doppler flowmetry. Electrical stimulation (ES) of sympathetic nerves originating in superior cervical ganglion (SCG) and topical nicotine (10-30 μM) onto BA of WKY significantly increased BABF. Both increases were inhibited by tetrodotoxin, 7-nitroindazole (neuronal nitric oxide synthase inhibitor), and ICI-118,551 (β(2)-adrenoceptor antagonist), but not by atenolol (β(1)-adrenoceptor antagonist). Topical norepinephrine onto BA also increased BABF, which was abolished by atenolol combined with 7-nitroindazole or ICI-118,551. Similar results were found in prehypertensive SHR. However, in adult SHR and RHR, ES of sympathetic nerves or topical nicotine caused minimum or no increase of BABF. It is concluded that excitation of sympathetic nerves to BA in WKY causes parasympathetic nitrergic vasodilation with increased BABF. This finding indicates an endowed functional neurogenic mechanism for increasing the BABF or brain stem blood flow in coping with increased local sympathetic activities in acutely stressful situations such as the "fight-or-flight response." This increased blood flow in defensive mechanism diminishes in genetic and nongenetic hypertensive rats due most likely to decreased parasympathetic nitrergic nerve terminals.     

Angiotensin-(1–7) in Paraventricular Nucleus Modulates Sympathetic Activity and Cardiac Sympathetic Afferent Reflex in Renovascular Hypertensive Rats

Background

Excessive sympathetic activity contributes to the pathogenesis and progression of hypertension. Enhanced cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation. This study was designed to determine the roles of angiotensin (Ang)-(1–7) in paraventricular nucleus (PVN) in modulating sympathetic activity and CSAR and its signal pathway in renovascular hypertension.

Methodology/Principal Findings

Renovascular hypertension was induced with two-kidney, one-clip method. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and cervical-vagotomized rats with anesthesia. CSAR was evaluated with the RSNA and MAP responses to epicardial application of capsaicin. PVN microinjection of Ang-(1–7) and cAMP analogue db-cAMP caused greater increases in RSNA and MAP, and enhancement in CSAR in hypertensive rats than in sham-operated rats, while Mas receptor antagonist A-779 produced opposite effects. There was no significant difference in the angiotensin-converting enzyme 2 (ACE2) activity and Ang-(1–7) level in the PVN between sham-operated rats and hypertensive rats, but the Mas receptor protein expression in the PVN was increased in hypertensive rats. The effects of Ang-(1–7) were abolished by A-779, adenylyl cyclase inhibitor SQ22536 or protein kinase A (PKA) inhibitor Rp-cAMP. SQ22536 or Rp-cAMP reduced RSNA and MAP in hypertensive rats, and attenuated the CSAR in both sham-operated and hypertensive rats.

Conclusions

Ang-(1–7) in the PVN increases RSNA and MAP and enhances the CSAR, which is mediated by Mas receptors. Endogenous Ang-(1–7) and Mas receptors contribute to the enhanced sympathetic outflow and CSAR in renovascular hypertension. A cAMP-PKA pathway is involved in the effects of Ang-(1–7) in the PVN.     

高血压大鼠不同血管平滑肌肌球蛋白磷酸化和脱磷酸化酶的变化

本文比较了正常和高血压大鼠不同动脉血管肌球蛋白轻链激酶（ＭＬＣＫ）和依赖Ｃａ＾２＋的钙调素磷酸酶（Ｃａ＾２＋／ＣａＭ－ＰＰ）活性的变化。结果表明：在自发性高血压大鼠（ＳＨＲ）不同血管ＭＬＣＫ的活性不同,依次为主动脉（Ａ）〉尾动脉（ＣＡ）〉肠系膜动脉（ＭＡ）;而在ＷＫＹ大鼠,该酶在不同血管的活性依次为Ａ〈〈ＣＡ〈〈ＡＭ。在ＷＫＹ大鼠,ＭＡ Ｃａ＾２＋／ＣａＭ－ＰＰ活性明显高于ＳＨＲ。在肾性高血压大鼠     

Sympathetic activity in early renal posttransplantation hypertension in rats

The contribution of elevated sympathetic activity to the development of renal posttransplantation hypertension was investigated. F1 hybrids (F1H) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were transplanted with either an SHR or an F1H kidney and bilaterally nephrectomized. Three weeks after transplantation, sympathetic activity was assessed by measuring adrenal tyrosine hydroxylase (TH) mRNA content and recording splanchnic nerve activity (SNA) in conscious animals. To investigate the dependence of arterial pressure on sympathetic activity, animals were treated with the alpha(2)-adrenoceptor agonist guanabenz intracerebroventricularly. Mean arterial pressure (MAP) was 143 +/- 4 mmHg in recipients of an SHR kidney (n = 15) versus 110 +/- 3 mmHg in recipients of an F1H kidney (n = 10; P < 0.001). Adrenal TH mRNA content was 1.93 +/- 0.15 fmol/microg total RNA in recipients of an SHR kidney versus 1.96 +/- 0.17 fmol/microg total RNA in recipients of an F1H kidney (not significant). SNA did not differ significantly between recipients of an SHR kidney (n = 8) and recipients of an F1H kidney (n = 7) in terms of frequency and amplitude of synchronized nerve discharges. In response to cumulative intracerebroventricular administration of 10 and 20 microg guanabenz, SNA fell to 51 +/- 5% of control in recipients of an SHR kidney versus 44 +/- 6% of control in recipients of an F1H kidney (not significant) accompanied by a slight fall in MAP in either group. The results suggest that elevated sympathetic activity is not a major contributor to the development of renal posttransplantation hypertension.     

Arterial Baroreceptor Reflex Counteracts Long-Term Blood Pressure Increase in the Rat Model of Renovascular Hypertension

Introduction

The present study tested the hypothesis that long-term effects of baroreceptor activation might contribute to the prevention of persistent arterial blood pressure (BP) increase in the rat model of renovascular hypertension (HTN).

Methods

Repetitive arterial baroreflex (BR) testing was performed in normo- and hypertensive rats. The relationship between initial arterial BR sensitivity and severity of subsequently induced two-kidney one-clip (2K1C) renovascular HTN was studied in Wistar rats. Additionally, the time course of changes in systolic BP (SBP) and cardiac beat-to-beat (RR) interval was studied for 8 weeks after the induction of 2K1C renovascular HTN in the rats with and without sinoaortic denervation (SAD). In a separate experimental series, cervical sympathetic nerve activity (cSNA) was assessed in controls, 2K1C rats, WKY rats, and SHR.

Results

The inverse correlation between arterial BR sensitivity and BP was observed in the hypertensive rats during repetitive arterial BR testing. The animals with greater initial arterial BR sensitivity developed lower BP values after renal artery clipping than those with lower initial arterial BR sensitivity. BP elevation during the first 8 weeks of renal artery clipping in 2K1C rats was associated with decreased sensitivity of arterial BR. Although SAD itself resulted only in greater BP variability but not in persistent BP rise, the subsequent renal artery clipping invariably resulted in the development of sustained HTN. The time to onset of HTN was found to be shorter in the rats with SAD than in those with intact baroreceptors. cSNA was significantly greater in the 2K1C rats than in controls.

Conclusions

Arterial BR appears to be an important mechanism of long-term regulation of BP, and is believed to be involved in the prevention of BP rise in the rat model of renovascular HTN.     

Inhibition of neurons in commissural nucleus of solitary tract reduces sympathetic nerve activity in SHR

Neurons in the commissural nucleus of the solitary tract (commNTS) play an important role in certain cardiovascular responses dependent on sympathetic vasoconstrictor activation, including the arterial chemoreceptor reflex. Electrolytic lesions of the commNTS elicit a fall in arterial pressure (AP) in spontaneously hypertensive rats (SHR). To determine whether the latter result 1) arose from elimination of commNTS neuronal activity rather than en passant axons and 2) was accompanied by a reduction in sympathetic nerve activity, we evaluated the effect of inhibition of neurons in the commNTS on basal splanchnic sympathetic nerve activity (SNA), AP, and heart rate (HR) in SHR, Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. In chloralose-anesthetized, paralyzed, and artificially ventilated SHR, microinjection of GABA into the commNTS markedly decreased splanchnic SNA, AP, and HR. The reductions in SNA and AP following similar microinjections in WKY and SD rats were significantly less than those in SHR. Our findings suggest that tonically active neurons in the commNTS contribute to the maintenance of SNA and the hypertension in SHR. The level of tonic discharge of these commNTS neurons in normotensive WKY and SD rats may be lower than in SHR.     

Superoxide anions in the paraventricular nucleus mediate the enhanced cardiac sympathetic afferent reflex and sympathetic activity in renovascular hypertensive rats

An enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation in renovascular hypertension. The present study was designed to determine the role of superoxide anions in the paraventricular nucleus (PVN) in mediating the enhanced CSAR and sympathetic activity in renovascular hypertension in the two-kidney, one-clip (2K1C) model. Sinoaortic denervation and vagotomy were carried out, and renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded under anesthesia. The CSAR was evaluated by the response of RSNA to the epicardial application of capsaicin. Superoxide anion levels and NAD(P)H oxidase activity in the PVN increased in 2K1C rats and were much higher in 2K1C rats than in sham-operated (sham) rats after the epicardial application of capsaicin or PVN microinjection of ANG II. In both 2K1C and sham rats, PVN microinjection of the superoxide anion scavenger tempol or the NAD(P)H oxidase inhibitor apocynin abolished the CSAR, whereas the SOD inhibitor diethyldithiocarbamic acid (DETC) potentiated the CSAR. Tempol and apocynin decreased but DETC increased baseline RSNA and MAP. ANG II in the PVN caused larger responses of the CSAR, baseline RSNA, and baseline MAP in 2K1C rats than in sham rats. The effects of ANG II were abolished by pretreatment with tempol or apocynin in both 2K1C and sham rats and augmented by DETC in the PVN in 2K1C rats. These results indicate that superoxide anions in the PVN mediate the CSAR and the effects of ANG II in the PVN. Increased superoxide anions in the PVN contribute to the enhanced CSAR and sympathetic activity in renovascular hypertension.     

Features of the behavior of the rat with hereditarily determined arterial hypertension

The behaviour of spontaneously hypertensive rats (SHR strain), rats with inherited stress induced arterial hypertension (ISIAH, a new developed strain), and of their normotensive Wistar progenitors was studied. The open-field arena and a device for measuring the total activity in the home cage were used in the behavioural studies. The SHR were much more active in the open--field and home cage tests than the Wistar and ISIAH rats. The basal locomotor activity of the ISIAH strain was lower than that of the Wistar rats, but the ISIAH strain had an index of behavioural reactivity 2.7 fold higher than the Wistar or SHR strains. These behavioural characteristics corresponded to the hypertension patterns of the strains compared. Enhanced spontaneous locomotion of the SHR rats was associated with spontaneous increase in arterial blood pressure. The ISIAH rats showed low spontaneous locomotor activity, but high behavioural and blood pressure reactivity under conditions of mild emotional stress.     

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood vessels to alter sympathetic outflow and hence blood pressure. Over 80% of bulbospinal, catecholaminergic (C1) neurons contain pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA. Activation of PACAP receptors with intrathecal infusion of PACAP-38 causes a robust, prolonged elevation in sympathetic tone. Given that a common feature of most forms of hypertension is elevated sympathetic tone, this study aimed to determine in the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (normotensive control) 1) the proportion of C1 neurons containing PACAP mRNA and 2) responsiveness to intrathecal PACAP-38. We further investigated whether intrathecal infusion of the PACAP antagonist, PACAP(6-38), reduces the hypertension in the SHR. The principal findings are that 1) the proportion of PACAP mRNA-containing C1 neurons is not different between normotensive and hypertensive rats, 2) intrathecal PACAP-38 causes a strain-dependent, sustained sympathoexcitation and tachycardia with variable effects on mean arterial pressure in normotensive and hypertensive rats, and 3) PACAP(6-38) effectively attenuated the effects of intrathecal PACAP-38, but had no effect alone, on any baseline variables. This finding indicates that PACAP-38 is not tonically released in the spinal cord of rats. A role for PACAP in hypertension in conscious rats remains to be determined.     

Role of autonomic nervous system on heart rate in experimental hypertension

Heart rate and the role of the autonomic nervous system in hypertensive conscious rats by subtotal nephrectomy were studied. Heart rate is significantly higher in the hypertensive rats. Sympathetic blockade with an intravenous injection of propranolol produces a higher decrease in heart rate of hypertensive rats than in control rats. Intravenous injection of atropine produces an increase in heart rate in both groups of animals. It is significantly higher in the control rats than in hypertensive animals. When the autonomic nervous system is blocked with atropine and propranolol, intrinsic heart rate is similar in both groups of animals. Similar results are obtained after blocking ganglionic transmission with hexamethonium. No significative differences are observed in heart rate after intracerebroventricular injection of hemicholinium-3 between both groups of rats. Results show an increased cardiac sympathetic tone, reduced parasympathetic activities, no alterations in the pacemaker activity and implications of central acetylcholine. These alterations in the autonomic nervous system have an important role in the maintenance of elevated heart rate in this experimental model of arterial hypertension.     

Spontaneous hypertension is primarily the result of sympathetic overactivity and immunologic dysfunction

Overactivity of the sympathetic nervous system and immunologic dysfunction have been shown to contribute to development and maintenance of hypertension in the Okamoto spontaneously hypertensive rat (SHR). In this study, the combined effects of reduction in sympathetic activity and immunologic manipulation on spontaneous hypertension have been determined. Neonatal SHRs received sham implants or implants of thymic tissue from Wistar donor rats. In addition, the thymus-implanted SHRs underwent bilateral renal denervation when they were 6 weeks old. At the same time, the sham-implanted SHRs underwent sham renal denervation. The denervations or sham operations were repeated when the SHRs were 9, 12, 15, and 18 weeks old. Wistar-Kyoto (WKY) rats also underwent serial sham renal denervations. Tail-cuff pressure measurements indicated that approximately 75% of the chronic hypertension in the SHRs was prevented by the combination of thymic implants and renal denervations. Direct arterial pressure measurements confirmed these results; when the rats were 21 weeks old, mean arterial pressure averaged 177 +/- 5.5 mm Hg in sham-operated SHRs, 134 +/- 2.7 mm Hg in implanted, denervated SHRs, and 121 +/- 2.1 mm Hg in sham-operated WKY rats. These data indicate that overactivity of the sympathetic nervous system and immunologic dysfunction account for the majority of the hypertension in the Okamoto SHR.     

Rostral ventral medulla 5-HT1A receptors selectively inhibit the somatosympathetic reflex

The role of the 5-hydroxytryptamine (5-HT1A) receptors in the rostral ventrolateral medulla (RVLM) on somatosympathetic, baroreceptor, and chemoreceptor reflexes was examined in anesthetized rats. Microinjection of the selective 5-HT1A agonist 8-hydroxy-di-n-propylamino tetralin (8-OH-DPAT) decreased arterial blood pressure and splanchnic sympathetic nerve activity (SNA). Electrical stimulation of the hindlimb evoked early and late excitatory sympathetic responses. Bilateral microinjection in the RVLM of 8-OH-DPAT markedly attenuated both the early and late responses. This potent inhibition of the somatosympathetic reflex persisted even after SNA and arterial blood pressure returned to preinjection levels. Preinjection of the selective 5-HT1A antagonist NAN-190 in the RVLM blocked the sympathoinhibitory effect of 8-OH-DPAT and attenuated the inhibitory effect on the somatosympathetic reflex. 8-OH-DPAT injected in the RVLM did not affect baroreceptor or chemoreceptor reflexes. Our findings suggest that activation of 5-HT1A receptors in the RVLM exerts a potent, selective inhibition on the somatosympathetic reflex.     

alpha(2)-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

We examined the effect of alpha(2)-adrenoreceptor blockade in the nucleus of the solitary tract (NTS) on baroreflex responses elicited by electrical stimulation of the left aortic depressor nerve (ADN) in urethane-anesthetized spontaneously hypertensive rats (SHR, n = 11) and normotensive Wistar-Kyoto rats (WKY, n = 11). ADN stimulation produced a frequency-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). In SHR, unilateral microinjection of idazoxan into the NTS markedly reduced baroreflex control of MAP, RSNA, and HR and had a disproportionately greater influence on baroreflex control of MAP than of RSNA. In WKY, idazoxan microinjections did not significantly alter baroreflex function relative to control vehicle injections. These results suggest that baroreflex regulation of arterial pressure in SHR is highly dependent on NTS adrenergic mechanisms. The reflex regulation of sympathetic outflow to the kidney is less influenced by the altered alpha(2)-adrenoreceptor mechanisms in SHR.     

Insulin-exacerbated hypertension in captopril-treated spontaneously hypertensive rats: role of sympathoexcitation

Insulin excess exacerbates hypertension in spontaneously hypertensive rats (SHR). This study examined the relative contribution of the renin-angiotensin system and the sympathetic nervous system in this phenomenon. In SHR, daily subcutaneous injections of insulin were initiated either before short-term angiotensin-converting enzyme inhibition with captopril or after lifetime captopril treatment. Insulin treatment resulted in significant increases in mean arterial pressure and heart rate and captopril treatment lowered arterial pressure, but captopril did not lower arterial pressure more in the insulin-treated compared with control rats. To test the contribution of the sympathetic nervous system to this form of hypertension, each rat was intravenously infused with either a ganglionic blocker (i.e., hexamethonium) or a centrally acting alpha2-adrenergic receptor agonist (i.e., clonidine). Administration of either agent largely eliminated the differences in mean arterial pressure and heart rate between the insulin-treated and saline-treated SHR, irrespective of captopril treatment. These data indicate that in SHR, the ability of insulin to increase blood pressure is closely related to sympathoexcitation, which is unresponsive to blockade of angiotensin-converting enzyme.