[A COMPARATIVE STUDY OF CATECHOLAMINERGIC AND NITROXIDERGIC VASOMOTOR NEURONS IN THE NUCLEI OF THE CAUDAL PART OF THE BRAINSTEM OF THE RAT].

Immunohistochemical methods for the demonstration of tyrosine hydrolase (TH) and neuronal form of nitric oxide synthase (nNOS) were used to study the distribution of catecholaminergic and nitroxidergic vasomotor neurons respectively, in the nuclei of the medulla oblongata and the pons of 12 Wistar rats. Most often the expression of TG was found in neurons located in the nucleus and several reticular nuclei (gigantocellular, paragigantocellular, caudal pons nucleus), but the proportion of immunoreactive neurons did not exceed 8-14%. In the other nuclei (reticular parvocellular nucleus and oral pons nucleus, spinal nucleus of the trigeminal nerve) the value of this parameter ranged from 1 to 3%. In a large group of nuclei with proven vasomotor function such neurons were constantly not detected. In the structures with high content of catecholaminergic neurons, nNOS-positive cells were found, as a rule, in fewer numbers than in the nuclei with a limited number of TH-positive neurons.

[Immunolocalization of hemeoxygenase-2 in neurons of the human vasomotor center in arterial hypertension].

We studied the immunolocalization of hemeoxygenase-2 in neurons of the medulla oblongata in men (n=8), aged 18-44 years, who died from causes unrelated to the injury of the central nervous system and in people with the lifetime diagnosis of hypertension (n=6). It has been found that neurons with enzyme positive reaction are present in all parts of the medulla oblongata with concentrations ranging from 0.5 to 13.7% of the total number of cells. The high proportion of small neurons with the high or moderate density of deposits was found in the sensory nuclei. Large cells of the motor nuclei often exhibit the negative or low intensity of the enzymatic reaction. In arterial hypertension, a decrease in the proportion AH NO-positive neurons and the average optical density of the reaction product was noted. The reduction was seen in most affected neurons in the rostral part of the solitary tract nucleus and the lateral reticular nucleus. In the motor nuclei and in the dorsal nucleus of the vagus nerve, these parameters decreased as well although the reduction was not as great as observed in the sensory nuclei.

Myeloperoxidase deficiency preserves vasomotor function in humans.

AIMS: Observational studies have suggested a mechanistic link between the leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we tested whether MPO is systemically affecting vascular tone in humans. METHODS AND RESULTS: A total of 12 135 patients were screened for leucocyte peroxidase activity. We identified 15 individuals with low MPO expression and activity (MPO(low)), who were matched with 30 participants exhibiting normal MPO protein content and activity (control). Nicotine-dependent activation of leucocytes caused attenuation of endothelial nitric oxide (NO) bioavailability in the control group (P < 0.01), but not in MPO(low) individuals (P = 0.12); here the MPO burden of leucocytes correlated with the degree of vasomotor dysfunction (P = 0.008). To directly test the vasoactive properties of free circulating MPO, the enzyme was injected into the left atrium of anaesthetized, open-chest pigs. Myeloperoxidase plasma levels peaked within minutes and rapidly declined thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior descending artery and the internal mammary artery (IMA) as well as myocardial perfusion decreased following MPO injection when compared with albumin-treated animals (P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed markedly diminished relaxation in response to acetylcholine (P < 0.01) and nitroglycerine as opposed to controls (P < 0.001). CONCLUSION: Myeloperoxidase elicits profound effects on vascular tone of conductance and resistance vessels in vivo. These findings not only call for revisiting the biological functions of leucocytes as systemic and mobile effectors of vascular tone, but also identify MPO as a critical systemic regulator of vasomotion in humans and thus a potential therapeutic target.

[Nitricoxideergic neurons of the human bulbar vasomotor center in arterial hypertension].

The distribution of nitricoxideergic neurons and activity of neuronal NO-synthase (nNOS) was studied in some nuclei of the medulla oblongata in patients with the lifetime diagnosis of arterial hypertension, stages I-III (AG I-III). In AG I, the significant decrease of nNOS activity was observed in most nuclei, although the relative content of NO-neurons was not changed. The marked changes of these parameters were noted in the nucleus of solitary tract compared to those of the reticular formation. In AG II, a portion NO-neurons in the nuclei was markedly reduced, however the following decrease of nNOS activity was not found. In AG III, there was the augmentation of nNOS activity and the subtle decrease in the portion of NO-neurons. Therefore, in AG, there is the decrease of quantitative parameters that characterize the state of the oxide-ergic system. This is one of the causes of the hyperactivation of sympathetic nervous system and elevation of arterial pressure. The exception is the dorsal nucleus of the vagus nerve, in which the relatively larger number of NO-neurons and higher nNOS activity were found, that may be related with the cholinergic mechanism of compensatory activation of the nitric oxide-ergic system.

High blood pressure arising from a defect in vascular function.

Hypertension, a major cardiovascular risk factor and cause of mortality worldwide, is thought to arise from primary renal abnormalities. However, the etiology of most cases of hypertension remains unexplained. Vascular tone, an important determinant of blood pressure, is regulated by nitric oxide, which causes vascular relaxation by increasing intracellular cGMP and activating cGMP-dependent protein kinase I (PKGI). Here we show that mice with a selective mutation in the N-terminal protein interaction domain of PKGIalpha display inherited vascular smooth muscle cell abnormalities of contraction, abnormal relaxation of large and resistance blood vessels, and increased systemic blood pressure. Renal function studies and responses to changes in dietary sodium in the PKGIalpha mutant mice are normal. These data reveal that PKGIalpha is required for normal VSMC physiology and support the idea that high blood pressure can arise from a primary abnormality of vascular smooth muscle cell contractile regulation, suggesting a new approach to the diagnosis and therapy of hypertension and cardiovascular diseases.

Influence of hyperoxia on skin vasomotor control in normothermic and heat-stressed humans.

Hyperoxia induces skin vasoconstriction in humans, but the mechanism is still unclear. In the present study we examined whether the vasoconstrictor response to hyperoxia is through activated adrenergic function (protocol 1) or through inhibitory effects on nitric oxide synthase (NOS) and/or cyclooxygenase (COX) (protocol 2). We also tested whether any such vasoconstrictor effect is altered by body heating. In protocol 1 (n = 11 male subjects), release of norepinephrine from adrenergic terminals in the forearm skin was blocked locally by iontophoresis of bretylium (BT). In protocol 2, the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the nonselective COX antagonist ketorolac (Keto) were separately administered by intradermal microdialysis in 11 male subjects. In the two protocols, subjects breathed 21% (room air) or 100% O(2) in both normothermia and hyperthermia. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure measured by Finapres. In protocol 1, breathing 100% O(2) decreased (P < 0.05) CVC at the BT-treated and at untreated sites from the levels of CVC during 21% O(2) breathing both in normothermia and hyperthermia. In protocol 2, the administration of l-NAME inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in both thermal conditions. The administration of Keto inhibited (P < 0.05) the reduction of CVC during 100% O(2) breathing in hyperthermia but not in normothermia. These results suggest that skin vasoconstriction with hyperoxia is partly due to the decreased activity of functional NOS in normothermia and hyperthermia. We found no significant role for adrenergic mechanisms in hyperoxic vasoconstriction. Decreased production of vasodilator prostaglandins may play a role in hyperoxia-induced cutaneous vasoconstriction in heat-stressed humans.

Vasomotor control in mice overexpressing human endothelial nitric oxide synthase.

Nitric oxide (NO) plays a key role in regulating vascular tone. Mice overexpressing endothelial NO synthase [eNOS-transgenic (Tg)] have a 20% lower systemic vascular resistance (SVR) than wild-type (WT) mice. However, because eNOS enzyme activity is 10 times higher in tissue homogenates from eNOS-Tg mice, this in vivo effect is relatively small. We hypothesized that the effect of eNOS overexpression is attenuated by alterations in NO signaling and/or altered contribution of other vasoregulatory pathways. In isoflurane-anesthetized open-chest mice, eNOS inhibition produced a significantly greater increase in SVR in eNOS-Tg mice compared with WT mice, consistent with increased NO synthesis. Vasodilation to sodium nitroprusside (SNP) was reduced, whereas the vasodilator responses to phosphodiesterase-5 blockade and 8-bromo-cGMP (8-Br-cGMP) were maintained in eNOS-Tg compared with WT mice, indicating blunted responsiveness of guanylyl cyclase to NO, which was supported by reduced guanylyl cyclase activity. There was no evidence of eNOS uncoupling, because scavenging of reactive oxygen species (ROS) produced even less vasodilation in eNOS-Tg mice, whereas after eNOS inhibition the vasodilator response to ROS scavenging was similar in WT and eNOS-Tg mice. Interestingly, inhibition of other modulators of vascular tone [including cyclooxygenase, cytochrome P-450 2C9, endothelin, adenosine, and Ca-activated K(+) channels] did not significantly affect SVR in either eNOS-Tg or WT mice, whereas the marked vasoconstrictor responses to ATP-sensitive K(+) and voltage-dependent K(+) channel blockade were similar in WT and eNOS-Tg mice. In conclusion, the vasodilator effects of eNOS overexpression are attenuated by a blunted NO responsiveness, likely at the level of guanylyl cyclase, without evidence of eNOS uncoupling or adaptations in other vasoregulatory pathways.

Neuroprotective role of coenzyme Q10 against dysfunction of mitochondrial respiratory chain at rostral ventrolateral medulla during fatal mevinphos intoxication in the rat.

We evaluated the functional changes in the mitochondrial respiratory chain at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, in an experimental model of fatal organophosphate poisoning using the insecticide mevinphos (Mev). We also investigated the neuroprotective role of coenzyme Q10 (CoQ10) in this process. Intravenous administration of Mev (1 mg/kg) in Sprague-Dawley rats maintained with propofol elicited an initial hypertension followed by hypotension, accompanied by bradycardia, with death ensuing within 10 min. Enzyme assay revealed a significant depression of the activity of nicotinamide adenine dinucleotide cytochrome c reductase, succinate cytochrome c reductase, and cytochrome c oxidase in the RVLM during this fatal Mev intoxication. ATP production also underwent a significant decrease. Pretreatment by microinjection bilaterally of CoQ10 (4 microg) into the RVLM significantly prevented mortality, antagonized the cardiovascular suppression, and reversed the depressed mitochondrial respiratory enzyme activities, or reduced ATP production in the RVLM induced during Mev intoxication. Our results indicated that dysfunction of mitochondrial respiratory chain and energy production at the RVLM takes place during fatal Mev intoxication. We further demonstrated that CoQ10 provides neuroprotection against Mev-induced cardiovascular depression and fatality through maintenance of activity of the key mitochondrial respiratory enzymes in the RVLM.

[Inhibition of adenosine deaminase activity by drugs influencing the cardiovascular system]. / Hamowanie deaminazy adenozyny przez leki wplywajace na uklad sercowo-naczyniowy.

Adenosine deaminase (ADA) is an unique enzyme which catalyzes conversion of adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine respectively. One of physiological roles of this enzyme is modulation of its substrate--adenosine concentration (both intracellular and extraectocellular). In presented work the influence of acetylsalicylic acid, metoprolol, simvastatin, isosorbide mononitrate and molsidomine on total activity of adenosine deaminase and its isoenzymes--ADA1 and ADA2 in vivo was studied. We have affirmed that simvastatin decreased of tADA activity by 50%, acetylsalicylic acid by 34%, metoprolol by 29.1% and isosorbide mononitrate by 19.3%. Only after molsidomine administration were no significant changes in ADA activity observed. The result showed that the decline of ADA activity was mainly due to marked decrease in ADA2 isoenzyme.

Gene-targeted mice reveal a critical role for inducible nitric oxide synthase in vascular dysfunction during diabetes.

BACKGROUND AND PURPOSE: Inducible nitric oxide synthase (iNOS) is a mediator of vascular dysfunction during inflammation. The purpose of this study was to test the hypothesis that vascular dysfunction during diabetes is dependent on expression of iNOS. METHODS: Diabetes was produced in mice with streptozotocin (150 mg/kg IP). After 4 to 6 months of diabetes, vasomotor function was examined in vitro in carotid arteries from mice with targeted disruption of the gene for iNOS (iNOS-deficient mice) and from normal, wild-type (WT) mice. RESULTS: Contractile responses of carotid arteries to U46619, a thromboxane A2 analogue, were not altered by diabetes in WT mice. Responses to U46619 were increased in arteries from diabetic iNOS-deficient mice compared with diabetic WT and nondiabetic mice (iNOS-deficient and WT mice). These results indicate that expression of iNOS inhibits an increased vasoconstrictor response during diabetes. Arteries from nondiabetic WT mice relaxed 83+/-2% (mean+/-SE) in response to acetylcholine (1 micromol/L) compared with 58+/-6% in arteries from diabetic WT mice (P<0.05 versus nondiabetic mice). In contrast, relaxation of carotid arteries to acetylcholine was similar (81+/-4% versus 76+/-6%; P>0.05) in iNOS-deficient mice under nondiabetic and diabetic conditions, respectively. Thus, diabetes produced impairment of endothelium-dependent relaxation in arteries from WT but not iNOS-deficient mice. Endothelium-independent relaxation in response to nitroprusside was similar in arteries from all mice. CONCLUSIONS: These results provide the first direct evidence that impairment of endothelium-dependent relaxation during diabetes is dependent on expression of iNOS.

Polymorphism in glutamate-cysteine ligase modifier subunit gene is associated with impairment of nitric oxide-mediated coronary vasomotor function.

BACKGROUND: The minor -588T allele of polymorphism -588C/T of a modifier subunit gene in glutamate-cysteine ligase (GCLM), a rate-limiting enzyme for glutathione (GSH) synthesis, was associated with lower plasma GSH levels and was a risk factor for myocardial infarction. METHODS AND RESULTS: We examined effects of the -588C/T polymorphism on coronary arterial diameter and blood flow responses to intracoronary infusion of acetylcholine in 157 consecutive subjects who had normal coronary angiograms. In multivariate linear regression analysis with covariates including traditional risk factors, the minor -588T allele had an independent association with impaired dilation or enhanced constriction of epicardial coronary arteries in response to acetylcholine, and it was independently associated with blunted increase in coronary flow response to acetylcholine. In a subgroup of 59 consecutive subjects, constrictor responses of epicardial coronary diameter to intracoronary infusion of NG-monomethyl-l-arginine, reflecting the presence of coronary nitric oxide (NO) bioactivity, had an inverse and independent association with the -588T allele in multivariate analysis. CONCLUSIONS: The -588T polymorphism of the GCLM gene causes a decrease in endothelial NO bioactivity, leading to impairment of endothelium-dependent vasomotor function in large and resistance coronary arteries. The GCL-GSH-NO axis may play a role in the defense system against coronary artery disease.

Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion.

Gap-junctional communication coordinates the behavior of individual cells in arterioles. Gap junctions are formed by connexins 40 (Cx40), Cx43, Cx37, and Cx45 in the vasculature. Previously, we have shown that lack of Cx40 impairs conduction of dilatory signals along arterioles. Herein, we examined whether hypertension is present in conscious animals and whether this is a direct effect or due to secondary mechanisms. Mean arterial pressure was elevated by 20-25 mmHg in conscious Cx40-deficient mice (Cx40(-/-)) compared with wild-type controls in both sexes. Differences in heart rate were not observed. Blockade of NO synthase increased pressure equally in both genotypes. Conversely, the angiotensin AT(1)-receptor antagonist, candesartan, decreased pressure to similar extents in Cx40(-/-) and wild-type mice. Acetylcholine and sodium nitroprusside (0.05-15 nmol) were equally potent and effective in decreasing pressure and inducing dilatory responses in the microcirculation. However, in contrast to wild type, Cx40(-/-) arterioles exhibited spontaneous, irregular vasomotion leading temporarily to complete vessel closure. We conclude that loss of Cx40 is associated with hypertension independent of the action of angiotensin II. It is also not related to an altered efficacy of NO or other endothelial dilators. However, the observed irregular vasomotion suggests that peripheral vascular resistance is affected.

Deficiency of glutathione peroxidase-1 sensitizes hyperhomocysteinemic mice to endothelial dysfunction.

OBJECTIVE: We tested the hypothesis that deficiency of cellular glutathione peroxidase (GPx-1) enhances susceptibility to endothelial dysfunction in mice with moderate hyperhomocysteinemia. METHODS AND RESULTS: Mice that were wild type (Gpx1+/+), heterozygous (Gpx1+/-), or homozygous (Gpx1-/-) for the mutated Gpx1 allele were fed a control diet or a high-methionine diet for 17 weeks. Plasma total homocysteine was elevated in mice on the high-methionine diet compared with mice on the control diet (23+/-3 versus 6+/-0.3 micromol/L, respectively; P<0.001) and was not influenced by Gpx1 genotype. In mice fed the control diet, maximal relaxation of the aorta in response to the endothelium-dependent dilator acetylcholine (10(-5) mol/L) was similar in Gpx1+/+, Gpx1+/-, and Gpx1-/- mice, but relaxation to lower concentrations of acetylcholine was selectively impaired in Gpx1-/- mice (P<0.05 versus Gpx1+/+ mice). In mice fed the high-methionine diet, relaxation to low and high concentrations of acetylcholine was impaired in Gpx1-/- mice (maximal relaxation 73+/-6% in Gpx1-/- mice versus 90+/-2% in Gpx1+/+ mice, P<0.05). No differences in vasorelaxation to nitroprusside or papaverine were observed between Gpx1+/+ and Gpx1-/- mice fed either diet. Dihydroethidium fluorescence, a marker of superoxide, was elevated in Gpx1-/- mice fed the high-methionine diet (P<0.05 versus Gpx1+/+ mice fed the control diet). CONCLUSIONS: These findings demonstrate that deficiency of GPx-1 exacerbates endothelial dysfunction in hyperhomocysteinemic mice and provide support for the hypothesis that hyperhomocysteinemia contributes to endothelial dysfunction through a peroxide-dependent oxidative mechanism.

Prostaglandin H synthase and vascular function.

Prostaglandin H synthase (PGHS) is a rate-limiting enzyme in the production of prostaglandins and thromboxane, which are important regulators of vascular function. Under normal physiological conditions, PGHS-dependent vasodilators (such as prostacyclin) modulate vascular tone. However, PGHS-dependent vasoconstriction (mediated by thromboxane and/or its immediate precursor, PGH(2)) predominates in some vascular pathologies (eg, systemic hypertension, diabetes, cerebral ischemia, and aging). This review will discuss the role of PGHS-dependent modulation of vascular function in a number of vascular beds (systemic, pulmonary, cerebral, and uterine) with an emphasis on vascular pathophysiology. Moreover, the specific contributions of the different isoforms (PGHS-1 and PGHS-2) are discussed. Understanding the role of PGHS in vascular function is of particular importance because they are the targets of the commonly used nonsteroidal antiinflammatory drugs (NSAIDs), which include aspirin and ibuprofen. Importantly, with the advent of specific PGHS-2 inhibitors for treatment of conditions such as chronic inflammatory disease, it is an opportune time to review the data regarding PGHS-dependent modulation of vascular function.

Evidence that Rho-kinase activity contributes to cerebral vascular tone in vivo and is enhanced during chronic hypertension: comparison with protein kinase C.

The small G protein Rho and its target Rho-kinase may participate in the mechanisms underlying vascular contractile tone via inhibition of myosin light chain phosphatase. The present study has tested the hypothesis that Rho-kinase activity normally contributes to cerebral vascular tone in vivo, and that this effect is augmented during chronic hypertension. Comparative studies also examined the role of protein kinase C (PKC) in regulation of cerebral artery tone. Two Rho-kinase inhibitors, Y-27632 (0.1 to 100 micromol/L) and HA1077 (1 to 10 micromol/L), caused marked concentration-dependent increases in basilar artery diameter of anesthetized normotensive rats (Sprague-Dawley and Wistar-Kyoto [WKY] strains), as measured using a cranial window approach. By comparison, the selective PKC inhibitors calphostin C (0.01 to 0.5 micromol/L) and Ro 31-8220 (5 micromol/L) had little or no effect on basilar artery diameter. Vasodilator responses to Y-27632 were unaffected by PKC inhibition or activation. In two models of chronic hypertension (spontaneously hypertensive rats and WKY rats treated with N-nitro-L-arginine methyl ester for 4 weeks), Y-27632 elicited cerebral vasodilator responses that were significantly greater than in control WKY rats (P<0.05), indicating that the chronically hypertensive state and not genetic factors contributed to the increased responses to Rho-kinase inhibition. PKC inhibition had no significant effect on basilar artery diameter in chronically hypertensive rats. These data suggest that Rho-kinase, but not PKC, activity contributes substantially to cerebral artery tone in vivo, and this effect is augmented in the cerebral circulation during chronic hypertension.

Molecular control of nitric oxide synthases in the cardiovascular system.

Nitric oxide plays an important role in cardiovascular homeostasis. In this review, the regulation of the three nitric oxide synthase isoforms in the cardiovascular system are examined at molecular and cellular levels. In addition, recent information gleaned from the use of NOS knockout mice are discussed.

[Pattern of distribution of constitutive isoforms of NO synthase in the normal prostate and obstructive prostatic hyperplasia]. / Verteilungsmuster der konstitutiven Isoformen der NO-Synthase in der normalen Prostata und der obstruktiven Prostatahyperplasie.

Nitric oxide (NO) is suggested as an important mediator for the regulation of biological processes. In the present study we tried to determine histochemically and immunohistochemically the localization and distribution of the constitutive NO-synthase Isoforms (bNOS and eNOS) of 14 normal non-obstructive and 12 hyperplastic obstructive human prostates. Differentiated nitrinergic innervation was shown for the prostate glands, fibromuscular stroma and blood vessels by NADPH-diaphorase staining and immunohistochemically with specific NOS antibodies. In the specimens with benign prostatic hyperplasia nitrinergic innervation seems to be distinctly reduced. The vascular distribution of NOS provides evidence for segmental differentiation of NO-mediated vascular regulation. The NADPH-diaphorase reaction was not confirmed immunohistochemically by the specific NOS antibody in the glandular epithelium. The distribution of NO synthase shows the importance of nitric oxide in the regulation of smooth muscle tone, blood flow and secretory function in the normal and hyperplastic human prostate.

Projections of nucleus paragigantocellularis lateralis to locus coeruleus and other structures in rat.

The projections of the retrofacial portion of nucleus paragigantocellularis lateralis (retrofacial PGCL) were mapped in the rat with the Phaseolus vulgaris leucoagglutinin anterograde tracing technique. This structure projects to a restricted number of bulbar or spinal nuclei involved in autonomic regulation, principally the intermediolateral cell column of the spinal cord, the nucleus tractus solitarius complex, the lateral parabrachial and Kolliker-Fuse nuclei and the ventrolateral medulla. Retrofacial PGCL also densely innervates the locus coeruleus. This projection originates in large part from phenylethanolamine-N-methyltransferase-immunoreactive cells (C1 adrenergic cluster) as demonstrated by immunohistochemistry combined with the retrograde transport of rhodamine-tagged microbeads. A very small suprabulbar projection of retrofacial PGCL was also detected in some cases.

[Functional activity of the structures of the medulla oblongata in rats with arterial hypertension of renal origin (histoenzymological research)]. / Funktsional'naia aktivnost' struktur prodolgovatogo mozga krys pri arterial'noi gipertenzii pochechnogo geneza (gistoénzimologicheskoe issledovanie).

A quantitative histochemical study of succinate dehydrogenase (SDH) and NADH-dehydrogenase (NADH-D) activity in medulla oblongata structures was accomplished in rats with arterial renovascular hypertension of the "2 kidneys-2 clips" type lasting 5 months. The systolic arterial blood pressure measured by the tail-cuff method was 179 +/- 4 mm Hg in hypertensive rats versus 108 +/- 3 mm Hg in control. There was a significant elevation of SDH activity in the ventral reticular and commissural nuclei, while in the neurons of the vagus dorsal and ambiguous nuclei it was lowered. NADH-D activity was significantly increased in the neuropil of the hypoglossal nerve nucleus and reduced in its neurons. The general trend was also revealed toward reduction of the maximal and elevation of the minimal activities in other nuclei. These metabolic alterations reflect changes in the functional activity of vasomotor and other structures of the medulla oblongata in renovascular hypertension.