Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats

Recent evidence in vivo indicates that spontaneously hypertensive rats (SHR) exhibit an increase in oxyradical production in and around microvascular endothelium. This study is aimed to examine whether xanthine oxidase plays a role in overproduction of oxidants and thereby may contribute to hypertensive states as a consequence of the increasing microvascular tone. The xanthine oxidase activity in SHR was inhibited by dietary supplement of tungsten (0.7 g/kg) that depletes molybdenum as a cofactor for the enzyme activity as well as by administration of (-)BOF4272 [(-)-8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo(1,5-alpha)-1,3, 5-triazine-4-monohydrate], a synthetic inhibitor of the enzyme. The characteristic elevation of mean arterial pressure in SHR was normalized by the tungsten diet, whereas Wistar Koto (WKY) rats displayed no significant alteration in the pressure. Multifunctional intravital videomicroscopy in mesentery microvessels with hydroethidine, an oxidant-sensitive fluoroprobe, showed that SHR endothelium exhibited overproduction of oxyradicals that coincided with the elevated arteriolar tone as compared with WKY rats. The tungsten diet significantly repressed these changes toward the levels observed in WKY rats. The activity of oxyradical-producing form of xanthine oxidase in the mesenteric tissue of SHR was approximately 3-fold greater than that of WKY rats, and pretreatment with the tungsten diet eliminated detectable levels of the enzyme activity. The inhibitory effects of the tungsten diet on the increasing blood pressure and arteriolar tone in SHR were also reproducible by administration of (-)BOF4272. These results suggest that xanthine oxidase accounts for a putative source of oxyradical generation that is associated with an increasing arteriolar tone in this form of hypertension.     

Hypercapnic cerebral blood flow in spontaneously hypertensive rats

OBJECTIVE: Hypercapnic cerebral vasodilation appears to be endothelium-dependent, as it involves nitric oxide and prostaglandins. Since chronic hypertension has been associated with impaired endothelial function, we designed a study to find out whether hypercapnic cerebral blood flow and its nitric oxide- and prostaglandin-sensitive component is reduced in spontaneously hypertensive rats (SHR) compared with normotensive controls. METHODS: Cerebral blood flow was measured in enflurane-anesthetized SHR (n=53), Wistar-Kyoto (WKY, n=20) and Sprague-Dawley (n=50) rats using the hydrogen clearance method. Cerebral blood flow was measured during eucapnia and hypercapnia; it was also assessed after administering either nonisoform-selective or isoform-selective neuronal nitric oxide synthase inhibitors and during inhibition of prostaglandin production. RESULTS: Hypercapnic cerebral blood flow did not differ among the strains. Nitric oxide synthase inhibition with intracortical N(G)-monomethyl-L-arginine reduced hypercapnic cerebral blood flow in SHR by 23+/-4% and in Sprague-Dawley rats by 23+/-7% without affecting eucapnic flow. Intraperitoneal administration of the inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduced eucapnic flow by 18+/-5% in SHR and 27+/-5% in WKY rats, and hypercapnic flow by 48+/-3 and by 51+/-6%, respectively. Indomethacin produced a similar decrease in hypercapnic flow in Sprague-Dawley rats and SHR (49+/-5 and 62+/-4%, respectively). CONCLUSION: Hypercapnic cerebral blood flow was not impaired in SHR. The contribution of nitric oxide- and prostaglandin-dependent vasodilation appeared to be intact Our results are consistent with the hypothesis that neuronal rather than endothelial production of nitric oxide may be responsible for maintaining hypercapnic cerebral vasodilation in SHR.     

Effects of clonidine and flesinoxan on blood pressure variability in conscious spontaneously hypertensive rats

Several species of scolopenders (Chilopoda: Scolopendridae), with their bites, are often cause of a local burning pain, redness, edema and sometimes leading to an erysipelas-like state. The present note deals with the main morphological characteristics useful for identificating of Scolopendra cingulata, the most common Italian species of Scolopendridae. Moreover, biology, ecology and medical aspects of the bite are discussed and two human cases due to S. cingulata bite occurred in Latium region (Italy) are described.     

Neurokinin-1 receptors and spinal cord control of blood pressure in spontaneously hypertensive rats

In this study we examined blood pressure and heart rate responses to intrathecal administration of a synthetic NK1-receptor agonist, H2N-(CH2)4-CO-Phe-Phe-Pro-NmeLeu-Met-NH2 (GR 73,632), in spontaneously hypertensive rats (SHR) and their progenitor strain, the Wistar-Kyoto rat (WKY). Sodium pentobarbitone anaesthetised rats with implanted intrathecal catheters were paralysed (pancuronium dibromide) and artificially ventilated. Injection of GR 73,632 at the T9 spinal level evoked dose-dependent increases in mean arterial pressure (MAP) in WKY and SHR. SHR had a lower MAP response threshold than WKY but increase in response with increasing dose was less in SHR than WKY. Biphasic blood pressure responses at high doses were observed in both strains. Prior administration of the NK1-receptor antagonist (3 aR,7aR)-7,7-diphenyl-2-[1-imino-2(methoxyphenyl)ethyl] perhydroisoindol-4-one (RP 67,580) significantly reduced the pressor response in WKY but not SHR. The depressor response was not attenuated in either strain.     

Altered permeability of the erythrocyte membrane for sodium and potassium ions in spontaneously hypertensive rats

Permeability of the erythrocyte membrane for sodium and potassium ions was studied in 8-10-week old spontaneously hypertensive rats (SHR, Kyoto Wistar strain), normotensive Wistar and Sprague-Dawley rats. The rate constnat of Na/Na exchange was considerably greater in the SHR than in the normotensive Wistar and Sprague-Dawley rats. This difference remained the same in the rats adrenalectomized 7 days prior to the experiment. The maximum difference in the constants was found when the sodium pump was blocked by ouabain. The accumulation of 42K in the erythrocytes of the SHR (the sodium pump being blocked) took place at a considerably slower rate, and the K+ washout into a potassium-free medium was faster than in the normotensive Wistar and Sprague-Dawley rats. These results seem to indicate a higher permeability of the SHR's erythrocyte membrane for Na+ and K+ ions, as compared to normotensive Wistar and Sprague-Dawley strains. It is suggested that the increased permeability of the erythrocyte membrane for Na+ and K+ in the SHR may reflect a more widespread cell membrane defect, which could serve as a general cause for activating the mechanisms maintaing high blood pressure.     

Intravenous injection with antisense oligodeoxynucleotides against angiotensinogen decreases blood pressure in spontaneously hypertensive rats

In the renin-angiotensin system, renin is known to cleave angiotensinogen to generate angiotensin I, which is the precursor of angiotensin II. Angiotensin II is a vasoactive peptide that plays an important role in blood pressure. On the other hand, the liver is the major organ responsible for the production of angiotensinogen in spontaneously hypertensive rats (SHR). To test the hypothesis that a reduction of angiotensinogen mRNA in the liver by antisense oligodeoxynucleotides (ODNs) may affect both plasma angiotensinogen and angiotensin II levels, as well as blood pressure, we intravenously injected antisense ODNs against rat angiotensinogen coupled to asialoglycoprotein carrier molecules, which serve as an important regulator of liver gene expression, into SHR via the tail vein. The SHR used in the present study were studied at 20 weeks of age and were fed a standard diet throughout the experiment. Plasma angiotensinogen, angiotensin II concentrations, and blood pressure all decreased from the next day until up to 5 days after the injection of antisense ODNs. These concentrations thereafter returned to baseline by 7 days after injection. A reduction in the level of hepatic angiotensinogen mRNA was also observed from the day after injection until 5 days after injection with antisense ODNs. However, in the SHR injected with sense ODNs, plasma angiotensinogen, angiotensin II concentrations, and blood pressure, as well as hepatic angiotensinogen mRNA, did not significantly change throughout the experimental period. Although the exact role of angiotensinogen in hypertension still remains to be clarified, these findings showed that intravenous injection with antisense ODNs against angiotensinogen coupled to asialoglycoprotein carrier molecules targeted to the liver could thus inhibit plasma angiotensinogen levels and, as a result, induce a decrease in blood pressure in SHR.     

Effect of endothelin-3 on blood pressure in conscious spontaneously hypertensive [SHR] and DOCA-salt hypertensive rats

The aim of the study was to investigate blood pressure responses and changes in heart rate after bolus administration of endothelin-3 [ET-3] in conscious, freely moving SHR and WKY rats and DOCA-salt hypertensive and normotensive Wistar rats. The effect of ET-3 on blood pressure and heart rats was investigated for four doses equal to 250 ng, 500 ng, 1000 ng and 2000 ng of ET-3. Our study shows that in experimental models of hypertension changes in blood pressure were predominantly characterized by the pronounced hypotensive phase with no significant raises in blood pressure. In normotensive animals cardiovascular responses to ET-3 were biphasic, with initial depressor phase followed by long-lasting, significant pressor effect.     

Relationship between nifedipine sensitivity of aortae and blood pressure of stroke-prone spontaneously hypertensive rats

1. We have previously described an increased sensitivity to inhibition by nifedipine of noradrenaline-induced contractures of blood vessels in hypertension. In this study we have investigated whether changes in blood pressure (BP) change the sensitivity to nifedipine and K+ of aortic rings from normotensive (Wistar-Kyoto rats, WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP were treated with: hydralazine plus hydrochlorothiazide; captopril plus hydrochlorothiazide; hydralazine plus guanethidine; or captopril alone. WKY rats were treated with deoxycorticosterone acetate (DOCA) and NaCl. Treatment commenced from 5 weeks of age and continued until 13-15 weeks. 3. The SHRSP treatments produced similar reductions in BP, and the BP of all the treated groups were significantly lower than the mean BP of untreated SHRSP (201.0 +/- 7.7 mmHg). The mean BP of the treated WKY rats (134.2 +/- 7.6 mmHg) was significantly higher than the mean BP of the untreated WKY rats (86.8 +/- 7.4 mmHg). 4. An area-under-curve (AUC) analysis of the inhibitory effects of nifedipine on responses of aortae to noradrenaline showed no differences between treated and untreated SHRSP groups (overall mean 40.6 +/- 1.9% and 43.4 +/- 3.4% inhibition of control AUC, respectively), or between DOCA-salt treated WKY and untreated WKY groups (58.8 +/- 5.9 and 64.8 +/- 2.3, respectively). Noradrenaline-induced contractures of aortae from all SHRSP groups were significantly more sensitive to inhibition by nifedipine than aortae from both WKY groups. 5. The molar concentration of agonist required to evoke 50% of the maximum response (EC50) values for potassium chloride (KCl) were significantly increased in the aortae of all treated SHRSP groups in comparison to those from untreated SHRSP (treated SHRSP groups, 15.53 +/- 0.68 mmol/L vs untreated SHRSP group, 11.36 +/- 1.10 mmol/L). The EC50 values for KCl for the aortae from the DOCA-treated WKY rats were significantly less than those from aortae of the untreated WKY (11.80 +/- 0.80 and 17.08 +/- 1.50 mmol/L, respectively). 6. We conclude that reduction (in SHRSP) or increase (in WKY) of the BP has no effect on the sensitivity of aortic smooth muscle to the inhibitory effects of nifedipine on responses to noradrenaline, suggesting that alterations in voltage-dependent Ca2+ mechanisms may be a primary phenomenon in the SHRSP. In contrast, the fact that sensitivity to KCl changes in the treated SHRSP and WKY aortae suggests such sensitivity is secondary to the BP and thus a separate phenomenon from voltage-dependent Ca2+ mechanisms.     

Tissue-specific regulation of angiotensinogen gene expression in spontaneously hypertensive rats

Angiotensinogen is expressed in many tissues besides the liver. Recent studies have suggested that abnormalities in the regulation of angiotensinogen gene expression may be involved in the development of hypertension. However, little information is available concerning the functional significance of tissue angiotensinogen. In this study, we measured plasma angiotensinogen concentration by radioimmunoassay and examined the expression of tissue angiotensinogen by Northern blot analysis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although plasma angiotensinogen concentration in SHR was comparable to that in WKY at 6 weeks of age, it was increased significantly at 14 weeks of age in SHR and became higher than that in WKY. The levels of hepatic angiotensinogen mRNA were similar in SHR and WKY, and the levels of aortic, adrenal, and renal angiotensinogen mRNAs were lower in SHR than in WKY at both 6 and 14 weeks of age. Brain angiotensinogen expression in SHR was higher than in WKY at 6 weeks of age and was comparable to that in WKY at 14 weeks of age. On the other hand, cardiac and fat angiotensinogen mRNA levels were significantly increased at 14 weeks of age in SHR. These results demonstrate that the expression of tissue angiotensinogen is regulated differently in SHR and WKY and indicate that the development of hypertension is accompanied at least temporally with increases in plasma angiotensinogen concentration as well as cardiac and adipogenic angiotensinogen mRNA in SHR.     

Role of nitric oxide in the control of blood pressure in young and adult spontaneously hypertensive rats

1. The depressor response to sodium nitroprusside (SNP) and the pressor response to Nomega-nitro-L-arginine methyl ester (L-NAME) were investigated in anaesthetized and ganglion-blocked 6 week old (young) and 20 week old (adult) spontaneously hypertensive rats (SHR), and the results were compared with those in age-matched normotensive Wistar-Kyoto (WKY) rats. 2. SNP produced a dose-dependent decrease of the mean blood pressure (BP) in both strains, and no differences in vascular sensitivity to SNP were observed between the strains. 3. L-NAME caused dose-dependent pressor responses in both strains. The sensitivity and the maximal response to L-NAME in SHR were significantly greater than those in age-matched WKY (P< 0.05 or 0.01; t-test, 13 d.f. in both ages). However, there were no significant differences in the responses between ages in each strain. 4. Acute reduction of BP induced by 7-O-ethylfangchinoline did not affect the responses to SNP and L-NAME in the adult SHR. 5. These results indicate that a greater amount of NO is tonically released in SHR and that its contribution to BP control is greater in SHR than in WKY, whereas vascular sensitivity to NO does not differ between the strains. In addition, acute changes in BP do not affect the degree of dependency on NO for BP control.     

Age and blood pressure related changes in cholesterol esterase activity and cholesterol content in aortas of stroke prone spontaneously hypertensive rats, spontaneously hypertensive rats and normotensive Wistar Kyoto rats

Changes in aortic lipolytic enzyme activities (cholesterol esterase and lipoprotein lipase) and acid phosphatase activity during aging were investigated in three strains of rats with different blood pressures; stroke prone spontaneously hypertensive rats (SHRSP), spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKR). The blood pressures of male, 7 month old animals, was 234 (SHRSP), 173 (SHR) and 128 (WKR) mmHg. The cholesterol esterase activity markedly decreased with age in the aortas of SHRSP, SHR and normotensive WKR rats, while acid phosphatase activity decreased only slightly, if at all, and lipoprotein lipase activity remained unchanged. This effect was enhanced by increasing blood pressure in SHRSP, SHR and WKR. The total aortic cholesterol content increased significantly with hypertension in a inverse relation with cholesterol esterase activity. These results suggest that cholesterol deposition in aged arteries is, at least partialy, ascribable to an age-related decrease in cholesterol esterase, and that hypertension aggravates the deposition of arterial cholesterol by accelerating the age-related decrease in aortic cholesterol esterase activity.     

Use of nonlinear methods to assess effects of clonidine on blood pressure in spontaneously hypertensive rats

In spontaneously hypertensive rats (SHR), chronic infusion of clonidine failed to decrease blood pressure and blood pressure variability. We used nonlinear methods to get a deeper insight on the effects of clonidine on blood pressure dynamics. For 24 h and 4 wk, clonidine (0.1 mg . kg-1 . day-1 sc) was infused by minipumps in the conscious SHRs, and, for comparison, a vehicle was infused in SHRs and in Wistar-Kyoto rats. Blood pressure was recorded for 30 min before and after treatments. We used the Lyapunov exponent, approximated by the inverse of the lmax index derived from the recurrence plot method, to characterize nonlinear dynamics. Before treatment, lmax index of blood pressure was lower (P < 0.01) in the SHRs than in the Wistar-Kyoto rats. Clonidine significantly increased lmax (P < 0.01) to the level observed in normotensive rats, at 24 h and up to 4 wk after infusion. We conclude that clonidine has a significant chronic effect on blood pressure dynamics, as evidenced by nonlinear methods. Our study also suggests that the mechanisms governing blood pressure variations are nonlinear.     

Autonomic control of heart rate and blood pressure in spontaneously hypertensive rats during aversive classical conditioning.

Examined heart rate (HR) and blood pressure (BP) responses of 26 spontaneously hypertensive rats (SHR) and 21 genetically-controlled Wistar/Kyoto (WKY) rats during aversive classical conditioning. Assessments were made of the effects of selective autonomic blockade by methyl atropine (10 mg/kg), phentolamine (2 mg/kg), and propranolol (2 mg/kg). The decelerative SHR HR CR was not secondary to baroreceptor reflex activity, although such activity was involved in the pressor BP and decelerative HR orienting response (OR) and UCR complex of the SHRs on initial applications of the CS and UCS. Augmented pressor BP ORs, CRs, and UCRs in the SHRs and differential drug effects on BP and HR baselines of the 2 strains suggested the presence of enhanced sympathetic activity in the SHRs that was not reflected in the SHR decelerative HR CR. Phentolamine unmasked evidence of reflex beta?-vasodilation deficiency in the SHRs that could have contributed to the enhancement of their BP OR and CR. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the brain renin-angiotensin system in the maintenance of blood pressure in conscious spontaneously hypertensive and sinoaortic baroreceptor-denervated rats

1. Evidence suggesting an involvement of the brain renin-angiotensin system (RAS) in the development/maintenance of hypertension in spontaneously hypertensive rats (SHR) relies, in part, on early experimental data reporting centrally mediated antihypertensive effects of saralasin. However, recent data using non-peptide AT1 receptor antagonists does not always support this theory because these compounds usually do not lower blood pressure when given centrally. 2. In the present study we have re-assessed the central effects of saralasin in conscious SHR as well as in sinoaortic baroreceptor-denervated (SAD) rats. Both of these models exhibit heightened sensitivity to the central pressor effects of angiotensin II (AngII) and, thus, any potential antihypertensive activity would provide functional evidence of activated brain RAS mechanisms in these models. 3. In SHR, saralasin failed to lower mean arterial pressure (MAP) when given intracerebroventricularly (i.c.v.) as bolus or infusion doses that blocked the centrally mediated pressor effect of AngII. 4. In SAD rats, there was a marked impairment of the baroreceptor-heart rate reflex function and enhanced centrally mediated pressor responses to AngII. However, i.c.v. saralasin infusions again did not alter MAP. 5. Collectively, these results suggest that the central RAS is not involved in the maintenance of MAP in SHR and SAD rats, both of which are models exhibiting a functional hyperresponsiveness to AngII.     

Altered beta-adrenergic regulation of Na-K-Cl cotransport in cultured smooth muscle cells from the aorta of spontaneously hypertensive rats. Role of the cytoskeleton network

To verify the hypothesis of Na-K-Cl cotransport (COTR) involvement in ion transport abnormalities as revealed in vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR), we compared the rate of ouabain-insensitive, bumetanide-inhibited 86Rb influx in quiescent and growing cultures of VSMC from the aorta of SHR and normotensive (BN.lx) rats and its regulation by the cAMP signaling system. Basal COTR was not altered in quiescent cells from SHR but was decreased by 30% to 40% (P < .02) in growing SHR VSMC as compared to BN.lx rats. In quiescent BN.lx VSMC, isoproterenol inhibited COTR by 50% and induced cell shape transition of > 90% of cells, resulting in the appearance of rounded VSMC with arborized cytoplasms. In contrast, isoproterenol elicited cell shape transition in only 50% of quiescent SHR VSMC and did not modify COTR. In growing cells, it decreased COTR by 85% to 95% and altered cell morphology in > 95% of VSMC without differences between SHR and BN.lx rats. Neither inhibitors of protein kinase A (H-89 and KT-5720) nor an inhibitor of phosphoprotein phosphatase (okadaic acid) affected cell shape transition and COTR suppression in isoproterenol-treated VSMC. The COTR suppression and cytoplasm arborization was also demonstrated by the addition of cytochalasin B, a disintegrator of microfilament bundles, and staurosporine, an inhibitor of protein kinase C. The effects of these compounds on COTR and SHR and BN.lx VSMC morphology were not different. The calmodulin antagonist R24571 decreased COTR by 60% to 70% in quiescent BN.lx VSMC and did not modify this carrier in SHR VSMC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chronic treatment with ME3221 on blood pressure and mortality in aged stroke-prone spontaneously hypertensive rats

1. The protective effect of ME3221, a surmountable AT1 antagonist, on the hypertension and its concomitant complications in aged (32 week old) stroke-prone spontaneously hypertensive rats (SHRSP) was studied following long-term (32 weeks) oral administration, and compared with those of losartan (metabolite EXP3174 is an insurmountable AT1 antagonist) and enalapril. 2. During the treatment period, ME3221, at a dose of 10 mg/kg per day steadily reduced the systolic blood pressure, and no tolerance was developed to the fall in blood pressure. The reference drugs showed similar activity, but the antihypertensive effect of ME3221 was more potent. 3. In the control group, rats began to die from 52 weeks of age and all rats had died by 64 weeks of age. In contrast, no rats treated with ME3221, losartan or enalapril died before 64 weeks of age. 4. ME3221, losartan and enalapril suppressed the hypertensive complications observed in control SHRSP, that is, cerebral apoplexy (stroke and cerebral oedema), renal injury (increased proteinuria, total N-acetyl-beta-D-glucosaminidase activity and ascites) and heart failure (cardiac hypertrophy and pleural effusion). 5. These results indicate that ME3221 has a stable anti-hypertensive effect, prevents hypertensive complications and prolongs survival in aged SHRSP equally as well as losartan and enalapril.     

Significance of the rate of systemic change in blood pressure on the short-term autoregulatory response in normotensive and spontaneously hypertensive rats

Cerebral autoregulation, the physiological regulatory mechanism that maintains a constant cerebral blood flow (CBF) over wide ranges of arterial blood pressure, was investigated in normotensive and spontaneously hypertensive rats by means of laser-Doppler flowmetry. Systemic arterial hypertension was produced at rates ranging from 0.02 mm Hg/second to 11 mm Hg/second by constant infusion of epinephrine and norepinephrine. Systemic arterial hypotension was produced at rates ranging from -0.03 mm Hg/second to -12 mm Hg/second, either by bleeding the animals into a reservoir or by compressing the abdomen. In those cases with a low rate of change in systemic arterial blood pressure (SABP), the measurements lasted for 5 +/- 2 minutes, and in those with a high rate of change in SABP, measurements lasted for 40 +/- 30 seconds. The purpose was to record the time of onset and course of autoregulation in the basal ganglia in response to slow or rapid changes in SABP. CBF in the basal gray matter remained at baseline values (i.e., autoregulation was functioning) if the rate of increase of SABP did not exceed a critical value (0.10 mm Hg/second in the normotensive rats; 0.35 mm Hg/second in the spontaneously hypertensive rats). When hypertension was produced at faster rates, CBF followed arterial blood pressure passively, and no autoregulatory response was observed for 2 +/- 1 minutes. Hypotension did not change the baseline CBF when it was not produced at a rate faster than -0.4 mm Hg/second in normotensive rats and -0.15 mm Hg/second in spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of bilateral lesions of the solitary tract nucleus on arterial blood pressure in spontaneously hypertensive rats of Okamoto strain

Bilateral electrolytic lesions of the solitary tract nucleus in control Wistar albino rats as well as in Okamoto rats with spontaneous arterial hypertension caused a considerable rise in the arterial blood pressure. Quantitative comparison of blood pressure rise in normotensive and hypertensive rats demonstrated that the rise in the systolic and mean blood pressure was not significantly different in both groups of animals. However, the rats with spontaneous hypertension reacted, with a greater rise in the diastolic pressure. A characteristic feature observed in the normotensive rats was a high rise in pulse pressure following lesion of the solitary tract nucleus while in the rats with spontaneous hypertension this change was not found. The authors conclude that increased peripheral vascular resistance in the rats with spontaneous hypertension is not due to inhibition or resetting of the baroreceptor reflex.