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Biomedical subjects

A K Johnson

Publications and source records attributed to A K Johnson.

At least 127 records · Page 7Linked to original sources

Role of arteria baroreceptor input on thirst and urinary responses to intracerebroventricular angiotensin II.

Intracerebroventricular (icv) infusion of angiotensin II (ANG II) in rats elicits greater water intake under hypotensive, compared with normotensive, conditions. The present experiments used sinoaortic baroreceptor-denervated (SAD) rats and sham-operated rats to examine if the modulatory effects of arterial blood pressure on water intake in response to icv ANG II are mediated by arterial baroreceptors. Mean arterial blood pressure (MAP) was raised or lowered by intravenous (i.v.) infusions of phenylephrine (1 or 10 micrograms.kg-1 x min-1) or minoxidil (25 micrograms.kg-1 x min-1), respectively. The angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) was infused i.v. to prevent the endogenous formation of ANG II during testing. Urinary excretion of water and solutes was measured throughout. Water intake elicited by icv ANG II was inversely related to changes in MAP. Specifically, rats drank more water in response to icv ANG II when MAP was reduced by minoxidil but drank less water when MAP was elevated by phenylephrine. The influence of changing MAP on the icv ANG II-induced drinking responses was not affected by SAD. These results suggest that the modulatory effects of arterial blood pressure on icv ANG II-induced drinking can occur in the absence of sinoaortic baroreceptor input.

Angiotensin II↗

Amastatin potentiates drinking elicited by osmotic stimuli: evidence for peptidergic mediation of intracellular dehydration-induced thirst.

Aminopeptidase inhibitors have been demonstrated to enhance the behavioral effects of both exogenously applied and endogenously released neuropeptides. In this study peptidase inhibitors were used as probes for involvement of central neuropeptides in osmotically-induced drinking behavior. Intracerebroventricular (i.c.v.) injections of amastatin, an aminopeptidase A inhibitor, potentiated water intake induced by subcutaneous injections of hypertonic saline. Drinking responses to i.c.v. infusions of hypertonic saline were also enhanced when amastatin was added to the infusions. The effect was not attenuated by the angiotensin receptor antagonist, [Sar1, Thr8]angiotensin II, which suggests that angiotensins do not play a role in the over-drinking. Drinking responses to centrally infused hypertonic saline were not enhanced by i.c.v. thiorphan, an endopeptidase inhibitor; this provides evidence that the effects of amastatin are specific for a particular class of peptidases. These results suggest that there is a role for an endogenous, non-angiotensinergic brain peptide in the mediation of osmotic thirst.

Aminopeptidases↗

The effects of ibotenate lesions of the median preoptic nucleus on experimentally-induced and circadian drinking behavior in rats.

Male Sprague-Dawley rats were injected with either ibotenic acid or vehicle in the region of the median preoptic nucleus (MnPO) during methoxyflurane anesthesia. Later, the rats were tested for drinking responses elicited by angiotensin II (1 and 2 mg/kg s.c.) and hypertonic saline (3 and 6% w/v s.c.). Tests were conducted at 3 different phases of a 12:12 light-dark (LD) cycle (in the middle of the light phase and in the early and midportion of the dark phase). The rats with ibotenate lesions of the MnPO drank significantly less than vehicle-injected and lesion control groups regardless of when the tests were conducted. Subsequent monitoring of the diurnal rhythm of drinking, employing electrical lickometers, detected no difference between the rhythms of 4 rats with ibotenate lesions of the MnPO who failed to drink to homeostatic challenges and 4 vehicle-injected control rats. The results indicate that ibotenic acid lesions of the MnPO block drinking behavior stimulated by angiotensin II and hypertonic saline without disrupting the entrainment or pattern of ad libitum drinking.

Angiotensin II↗

Regulation of sodium and body fluid homeostasis during development: implications for the pathogenesis of hypertension.

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.

Animals↗

Effects of a non-peptide angiotensin receptor antagonist on drinking and blood pressure responses to centrally administered angiotensins in the rat.

Both angiotensin II (ANG II) and angiotensin III (ANG III) administered centrally produce drinking and increases in blood pressure. The recent characterization of two subtypes for the ANG II receptor, the AT1 and AT2, raises the questions of whether drinking and pressor responses to ANG II can be separated pharmacologically and whether ANG III acts via the same receptor subtype. Therefore, the current study examined drinking and blood pressure responses to ANG II and ANG III administered centrally in adult male Sprague-Dawley rats in the presence or absence of a selective AT1 receptor antagonist. Blockade of the AT1 receptor abolished both drinking and pressor responses to ANG II and ANG III. However, drinking to the cholinergic agonist, carbachol, was unaffected. These results demonstrate that centrally administered ANG II and ANG III increase both water intake and blood pressure via the AT1 receptor subtype.

Angiotensin II↗

The effects of central norepinephrine infusions on drinking behavior induced by angiotensin after 6-hydroxydopamine injections into the anteroventral region of the third ventricle (AV3V).

Adult male Sprague-Dawley rats were injected with either 6-hydroxydopamine (6-OHDA) or vehicle in the median preoptic nucleus and the organum vasculosum of the lamina terminalis. The subjects were tested for drinking responses to intraventricular angiotensin II (ANG II) or saline during either saline or norepinephrine intraventricular infusions. Rats injected with 6-OHDA into the ventral lamina terminalis initially failed to show drinking responses to ANG II injections. However, norepinephrine infusion in combination with ANG II injection restored the drinking response to ANG II in rats with catecholamine depletions of the lamina terminalis region.

Angiotensin II↗

Dissociation of experimentally induced drinking behavior by ibotenate injection into the median preoptic nucleus.

Adult male Sprague-Dawley rats were injected with either ibotenic acid (5 micrograms/1 microliter) or vehicle in the ventral median preoptic nucleus. The injections were given during either methoxyflurane or ketamine anesthesia. None of the rats injected with ibotenic acid were adipsic after surgery. After at least one week of recovery, all rats were tested for drinking responses to angiotensin II (1.5 and 3 mg/kg s.c.) and hypertonic saline (3% and 12% 1 ml/100 g b.wt.). Rats injected with ibotenic acid during methoxyflurane anesthesia drank significantly less than the vehicle injected control group in tests with both doses of angiotensin II and both concentrations of hypertonic saline. The rats that were injected with ibotenic acid during ketamine anesthesia drank significantly less than the control group when tested with 3% hypertonic saline but not when tested with angiotensin II. Histological examination of the injection sites indicated significant reductions in the volume of the median preoptic nucleus only in rats that had been injected with ibotenic acid during methoxyflurane anesthesia. The results are consistent with the interpretation that the drinking response to angiotensin II is dependent upon the integrity of neurons with postsynaptic N-methyl-D-aspartate receptors within the median preoptic nucleus.

Analysis of Variance↗

Blood pressure, heart rate, and regional resistance in behavioral defense.

Rats were instrumented with arterial catheters and directional pulsed Doppler flow probes for measurement of arterial blood pressure, heart rate, and blood flow in the renal, mesenteric, and hindquarter vascular beds. When tested as intruders in a resident-intruder aggression test, subjects responded to resident attack with species-characteristic defensive behavior and the "defense reaction" pattern of increased heart rate, renal resistance, and mesenteric resistance, and decreased hindquarter resistance. Blood pressure was variable, but sustained increases in blood pressure were rarely observed. The maintenance of blood pressure during species-specific defensive behavior can be contrasted with the sustained pressor responses observed in the centrally elicited defense reaction. The combination of pulsed Doppler technology and the resident-intruder paradigm appears to be a promising method for investigating the mechanisms of cardiovascular adjustment to behavioral defense.

Aggression↗

Meal-related and rhythmic drinking: effects of abolition of rat's eating rhythm.

Eating and drinking in the rat, which are both highly rhythmic and nocturnal activities, are temporally and quantitatively associated. The present study abolished the rhythmicity of eating by temporally and quantitatively restricting food access to 12 equally sized bihourly meals daily (total food available was equal to 80% of daily ad libitum intake). Water access remained ad libitum and was monitored and quantified in terms of 1) nocturnality, 2) association with meals, and 3) changes in the association of food and water intake across the phases of the light-dark cycle. Similar parameters were obtained from the same rats with ad libitum access to both food and water. The results indicate that both rhythmic and meal-induced effects are detectable in the drinking of rats with restricted food access, although both the rhythmic and meal-associated factors are reduced compared with drinking under ad libitum food access. Most important, the data clearly demonstrate large changes in the association of food and water intake across the phases of the light-dark cycle. These findings indicate a complex interaction of meal-associated and rhythmic factors in the control of drinking.

Animals↗

Drinking after osmotic challenge depends on circadian phase in rats with free-running rhythms.

Rhythmic phase-dependent modulation of the amount of water intake of rats occurs after several types of dipsogenic treatments. Previous studies conducted on rats in light-dark cycles confound direct effects of the light-dark cycle with the effects of circadian rhythmicity entrained to the light-dark cycle. The present study isolates the effect of circadian phase on the amount of drinking induced by injection of hypertonic saline. Free-running rhythms were induced in rats, and then water intake was measured after injections of both hypertonic and isotonic saline at different phases of the rats' circadian cycle. After injections of hypertonic saline, rats drank more water in their active phase than in their inactive phase. No difference in the amount of intake was found in rats that received isotonic saline at different phases of their circadian rhythms. The results indicate a circadian modulation of the drinking induced by cellular dehydration.

Activity Cycles↗

Enhanced drinking after excitotoxic lesions of the parabrachial nucleus in the rat.

Previous reports indicate the lateral parabrachial nucleus (IPBN) is important in the regulation of fluid intake. After electrolytic lesions of the IPBN, rats consume increased amounts of water when challenged with pharmacological stimuli that mimic depletion of the extracellular fluid space. Nonetheless, it is possible that neurons within the IPBN are not responsible for the overingestion of water during extracellular thirst challenges, since electrolytic lesions damage fibers of passage as well as neurons within the IPBN. Thus we used the excitatory neurotoxin ibotenic acid to lesion cell bodies within the IPBN. After recovery from surgery, water consumption by lesioned rats was significantly greater than consumption by vehicle or uninjected control rats when challenged with subcutaneous angiotensin II or isoproterenol to stimulate drinking. However, when injected with subcutaneous hypertonic saline to produce cellular dehydration, or when water deprived for 24 h, the water intake of rats with lesions was not different from the intake of control rats. Anatomical examination of the lesion sites revealed that ibotenic acid injection caused a notable loss of neurons in the IPBN with little or no damage to surrounding structures. Moreover, injection of an anterograde tracer into the dorsomedial medulla resulted in labeling of fibers that traverse the ibotenic acid lesion site. Together, these data suggest neurons within the IPBN are involved in the regulation of fluid intake, particularly challenges that involve depletion of the extracellular fluid space.

Angiotensin II↗

Role of anteroventral third ventricle and vasopressin in renal response to stress in borderline hypertensive rats.

The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat. In response to acute environmental stress (air jet), the borderline hypertensive rat exhibits a diuretic response, whereas the parental strains exhibit an antidiuretic response (spontaneously hypertensive rat) or no change in urine flow rate (Wistar-Kyoto rat). This study sought to investigate the role of the periventricular tissue surrounding the anteroventral third ventricle and vasopressin release in the diuretic response of the borderline hypertensive rat to acute environmental stress. Sixteen-week-old borderline hypertensive rats who had consumed a 1% NaCl diet for 10-12 weeks were given either electrolytic lesions of the anteroventral portion of the third ventricle or sham lesions. When exposed to acute environmental stress 4 weeks later, the increase in volume of dilute urine seen in the sham-lesion rats was not observed in the lesion rats. Plasma vasopressin concentration was decreased by acute environmental stress in the sham-lesion rats (15.2 +/- 4.0 to 10.9 +/- 1.7 pg/ml, p less than 0.05) but was unchanged in the lesion rats (12.3 +/- 2.0 to 13.4 +/- 4.0 pg/ml). In a separate group of intact borderline hypertensive rats, a constant intravenous infusion of vasopressin prevented the diuretic response to acute environmental stress. The results suggest that acute environmental stress produces a diuresis in the borderline hypertensive rats via a decrease in plasma vasopressin concentration that is dependent on the integrity of the periventricular tissue of the anteroventral portion of the third ventricle.

Animals↗

The effects of exercise training on salt-induced hypertension in the borderline hypertensive rat.

The borderline hypertensive rat (BHR) develops severe hypertension when chronically subjected to either a high salt diet or behavioral stress. Previous research has shown that daily exercise can attenuate the development of stress-induced hypertension in the BHR. The current study sought to determine whether exercise might also exert a similar protective effect on salt-induced hypertension. Two groups of BHR were placed on a high salt diet for 20 weeks; one of the groups also engaged in daily swim training for the entire 20 week period. A third group of BHR served as maturation controls. At the end of the experimental period, direct measurement of heart rate in conscious subjects revealed a significant resting bradycardia in the trained group on a high salt diet but no significant group differences with respect to blood pressure level. Cardiovascular responses to an episode of acute stress revealed that BHR are capable of elevating pressure in response to a novel stressor after swim training. These observations suggest that exercise may be an environmental intervention capable of increasing cardiovascular responses to acute stressors.

Animals↗

Beta-2 adrenoceptor mediated vasodilation: role in cardiovascular responses to acute stressors in spontaneously hypertensive rats.

The present paper summarizes our studies on the role of beta-2 adrenoceptor mediated vasodilatory mechanisms in the cardiovascular defense response of spontaneously hypertensive rats (SHR) and presents new data on the contribution of altered vascular responsiveness to vasodilators. SHR had similar blood pressure but exaggerated plasma norepinephrine (NE) and epinephrine (EPI) responses compared to their normotensive control strain, the Wistar-Kyoto (WKY), while the plasma catecholamine response of the first generation (F1) cross was intermediate. An examination of regional blood flow changes to footshock stress indicated that SHR compared to WKY had greater increases in mesenteric vascular resistance that appeared to be offset by more pronounced decreases in hindquarter vascular resistance. Blockade of beta-2 adrenoceptors, which are densely located in the skeletal muscle vasculature, led to greatly increased pressor responses to stress in SHR but was without effect in WKY. Results of our current work indicate that this response is due to increased stimulation of the beta-2 adrenoceptors during stress rather than to increased vascular reactivity. These results indicate that in SHR relative to WKY, the exaggerated sympatho-adrenal response to stress does not produce greater blood pressure responses because of the offsetting influences upon vasodilation and vasoconstriction.

Albuterol↗

Amastatin potentiation of drinking induced by blood-borne angiotensin: evidence for mediation by endogenous brain angiotensin.

Angiotensinergic synapses in the central nervous system (CNS) have been proposed to be involved in drinking induced by both intracerebroventricular (i.c.v.) and peripheral administration of angiotensins. In the present studies, we tested this hypothesis with i.c.v. application of amastatin, an aminopeptidase A inhibitor, to block peptide degradation. Potentiation of i.c.v. angiotensin II (Ang II)-induced drinking responses was observed when amastatin and Ang II were administered. Amastatin did not potentiate drinking to carbachol which demonstrates that the enhancement is specific to peptides. Centrally administered amastatin also potentiated drinking following systemic administration of Asn1 angiotensin II. (Asn1 Ang II). The results are consistent with the hypothesis that CNS angiotensin synapses are involved in the dipsogenic response that results from elevated levels of circulating angiotensin.

Aminopeptidases↗

Dam strain affects cardiovascular reactivity to acute stress in BHR.

The effect of maternal strain on reactivity to acute stress was studied in F1 reciprocals produced by crossing the spontaneously hypertensive rat (SHR) with its normotensive progenitor, the Wistar-Kyoto (WKY). This F1 generation, known as the borderline hypertensive rat (BHR), is genetically predisposed to develop hypertension in response to chronic stress or high dietary sodium. Reciprocals, considered to be genetically equivalent aside from sex-linked traits, differ in strain of dam during intrauterine and preweanling development. At 17 weeks of age, reciprocal F1 males did not differ in open-field behavior (squares crossed, rearings, and defecation measured over 3 days in 15-min sessions) or in home-cage measurements of mean arterial pressure (MAP) and heart rate (HR). However, different patterns of cardiovascular reactivity were displayed to transfer and footshock. While WKY-mothered rats reacted with graded pressor responses, SHR-mothered rats responded maximally to transfer, showed no additional increase to footshock, and maintained peak responding after footshock was terminated. Such reactivity differences may mediate the impact of environmental variables on the genetic disposition to hypertension.

Animals↗

Light/dark cycle modulates food to water intake ratios in rats.

Ad lib water intake of rats displays two prominent features: Water intake is temporally and quantitatively associated with food intake, and water intake is nocturnal. Physiological mechanisms linking water and food intake suggest that the rhythmicity in water intake may be at least partially driven by a rhythmicity in food intake. The present study examined whether the daily rhythm of rats modulates the association of food and water intake. Rats were housed under light/dark cycles and continuously monitored for temporal and quantitative patterns of ad lib food and water intake. The results indicate that the water/food ratio is much lower for meals consumed in the light phase than in the dark phase. The above results suggest a rhythmic modulation of the mechanisms linking food and water intake. We suggest that much of the complex rhythm of drinking stems from several interacting factors. 1) Food intake is nocturnal. 2) Food intake induces water intake by physiological mechanisms. 3) The amount of water intake induced by food intake is influenced by rhythmic factors.

Animals↗