Helmut Geiger

Neurotransmitters and Neuropeptides in the Baroreceptor Reflex Arc: Connections Between the Nucleus of the Solitary Tract and the Ventrolateral Medulla Oblongata in the Rat

The primary baroreceptor area (nucleus of the solitary tract-NTS) is anatomically interconnected with the rostral (vasomotor area) and the caudal (vasodepressor area) ventrolateral medulla by a well-defined arc of neuronal pathways. The chemical character and the direction of these pathways have been investigated with immunohistochemical and neurochemical techniques in intact and brainstem-operated rats. The transection of the neuronal arc resulted in an accumulation of tyrosine hydroxylase immunoreactivity in a small group of cells in the NTS adjacent to the area postrema, ipsilateral to the knife cut. Decreased angiotensinogen mRNA and atrial natriuretic peptide concentrations were measured in the ventrolateral medulla after the cut, and an accumulation of angiotensin II-immunoreactivity was found in neuronal perikarya in the ipsilateral NTS. Intracranial vagotomy caused marked depletions in glutamate levels in the subcommissural portion of the NTS and in the caudal ventrolateral medulla but nowhere else in the brainstem investigated including the rostral ventrolateral medulla.

Atrial natriuretic factor in specific brain areas of spontaneously hypertensive rats

Atrial natriuretic peptldes (atrial natriuretic factor, ANF) are present in a great number of brain areas inside and outside of the blood-brain barrier. The pattern of distribution implies the involvement of ANF in different physiological functions, such as blood pressure regulation, electrolyte and fluid bomeostasis, and modulation of the neuroendocrine system. To further investigate a possible involvement of central ANF in spontaneous hypertension, we measured levels of ANF in 18 selected, microdissected brain areas of prehypertensive (4-week-old) and hypertensive (12-week-oM) spontaneously hypertensive rats (SHR) and their normotensive control, Wistar-Kyoto rats (WKY), by radioimmunoassay. ANF was significantly decreased in seven brain areas in SHR at both ages investigated; the most pronounced decreases were found in the subfornical organ, in the perifornkal and periventricular hypothalamic nuclei, and in the medial preoptic nucleus. In addition, in young SHR ANF was significantly decreased in the organum vascutosum laminae terminalls and increased in the median eminence. After the development of hypertension, a significant decrease of ANF could be detected in four more brain areas (bed nucleus of the stria terminalis, paraventrkular and arcuate nuclei, dorsal raphe nucleus) of SHR, as compared with normotensive controls, and the increase in the median eminence was no longer detectable. These results suggest a role for ANF in genetk hypertension and the specific importance of certain brain regions.

Effects of Aldosterone and Dexamethasone on Atrial Natriuretic Peptide Levels in Preoptic and Hypothalamic Nuclei of Adrenalectomized and Intact Rats

The effect of aldosterone and dexamethasone on the concentrations of atrial natriuretic peptide (ANP) in preoptic and hypothalamic nuclei was examined in adrenalectomized and intact rats. Five days after adrenalectomy, increased ANP levels in those brain areas which control water intake, i.e. in the subfornical organ, supraoptic nucleus, and in the so-called hypothalamic drinking centers (perifornical nucleus, lateral hypothalamic area) were measured. In contrast to this, adrenalectomy decreased ANP levels markedly in the organum vasculosum laminae terminalis and preoptic periventricular nucleus, which are reportedly involved in the central regulation of salt and water homeostasis. ANP contents of these two preoptic structures were restored almost completely by daily administration of 0.9% sodium chloride or aldosterone but not dexamethasone. The daily administration of aldosterone elevated ANP levels in the supraoptic, paraventricular and perifornical nuclei as well as in the lateral hypothalamus both in control and adrenalectomized rats. Dexamethasone which was without any significant effect on preoptic and hypothalamic nuclei in control rats elevated ANP levels in the supraoptic and perifornical nuclei and in the lateral hypothalamic area of adrenalectomized animals. Since neither adrenalectomy, nor aldosterone or dexamethasone treatment influenced plasma ANP levels, altered ANP contents measured in preoptic and hypothalamic nuclei may represent a direct effect of adrenal corticoids (mainly aldosterone) on brain ANP-containing neurons which may participate in the control of body fluid and electrolyte homeostasis.

Glandular adenylate cyclase system in genetic hypertension: age-dependent response to catecholamines☆

The parotid excretion of cAMP was measured in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in this study. In addition, adenylate cyclase activity in parotid gland tissue was determined. The cAMP excretion rate was increased immediately after isoproterenol infusion. This elevation was more pronounced in young (6-8 weeks) than in older (16-18 weeks) animals, both in WKY and in SHR. These data demonstrate a diminished cAMP response to isoproterenol application with respect to the age of the animals. This could indicate that there is an age-dependent functional alteration of the beta-adrenoceptor-adenylate cyclase complex. In agreement with the results of these in vivo studies, the stimulation of adenylate cyclase activity of the parotid gland by isoproterenol or fluoride was enhanced in young SHR and lowered in old SHR when compared to their normotensive controls of the same age. One may conclude that the sympathetic activity is enhanced in young SHR, and that the beta-adrenoceptor system is hypersensitive to adrenoceptor agonists. This might contribute to the development of hypertension in SHR. Sixteen to eighteen weeks old SHR showed a diminished cAMP output following isoproterenol application when compared to normotensive control rats of the same age. The reduction of the response to isoproterenol stimulation in old SHR seems to be related to a reduced sensitivity to catecholamine stimulation.

Does cadmium contribute to the development of renal parenchymal hypertension

In our study we investigated 36 out-patients with renal disease, 22 of whom were hypertensive. In all patients proteinuria was present (4.30 ± 5.05 g protein/day) and kidney diseases were verified by renal biopsy. Blood cadmium in non-smokers was significantly (p< 0.05) lower than in smokers. We found a positive correlation between cadmium-concentration of blood and urine (p<0.01, R = 0.44) and between cadmium-concentration of blood and blood uric acid (p< 0.01, R = 0.44). Proteinuria was weakly correlated with cadmium concentration of urine (p<0.05, R = 0.35). Patients with renal hypertension showed a significantly higher (p< 0.05) urine cadmium excretion per day (1.60 ± 1.12 μg/day) compared to normotensives with a disease of the kidney (1.14 ± 1.47 μg/day). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.

EFFECT OF ANGIOTENSIN‐CONVERTING ENZYME INHIBITORS CAPTOPRIL AND ENALAPRIL ON cAMP CONTENT OF SPECIFIC BRAIN AREAS IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The influence of two angiotensin‐converting enzyme inhibitors, captopril and enalapril, on the cAMP content of microdissected brain areas was examined in spontaneously hypertensive rats. Both drugs depleted systolic arterial blood pressure significantly.

Participation of Various Brain Nuclei in the Altered Time Course of Genetic Hypertension in SHR Dependent on Changes in Calcium Metabolism

Variations in calcium alimentation influence the development of high blood pressure in genetic hypertensive rats. Different calcium feeding and changes in parathyroid hormone status cause altered cAMP-content in specific brain areas. All animals with high calcium diet show significant elevated cAMP-content in the locus coeruleus, irrespective of parathyroid status. These findings support the hypothesis that elevated cAMP-concentrations reflect an increased depressor activity of the locus coeruleus.

Effect of the ACE-Inhibitor Enalapril on Plasma Concentration of Atrial Natriuretic Peptide and on Glomerular Filtration Rate in Normotensive and Hypertensive Diabetic Rats

Earlier experimental data support the hypothesis that the atrial natriuretic peptide (ANP) is a potential mediator of glomerular hyperfiltration in diabetic rats. Several studies have shown that the renal hemodynamic and excretory responses to ANP are modulated by intrarenal angiotensin II. In the present study we investigated the effect of the angiotensin-converting (ACE)-inhibitor enalapril on plasma concentration of ANP and on glomerular filtration rate (GFR) both in normotensive diabetic rats and in diabetic rats with five-sixths renal ablation. We didn’t find a significant increase of plasma ANP in rats with moderate hyperglycemia. Treatment with enalapril significantly (p<0.05) decreased GFR both in control rats and in normotensive diabetic rats. Plasma concentration of ANP was significantly (p<0.001) decreased in five-sixths nephrectomized rats with diabetes mellitus by ACE-inhibiton. “Normalization” of plasma ANP in diabetic rats with renal ablation by enalapril treatment was positively correlated with a reduction of systolic blood pressure and with a decrease of body weight, while GFR.didn’t change under these conditions.