Robert F. Kirby

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.

The effects of caffeine on blood pressure and heart rate: A review

Concerns have been raised frequently about caffeine’s potential for increasing blood pressure (BP) and posing a risk for cardiovascular disease. This review surveys research concerning the effects of caffeine on BP and heart rate (HR). Tolerance to caffeine, family history of hypertension, borderline hypertension, and hypertension are also examined as potential moderators. Results from epidemiological studies are inconsistent. Experimental laboratory studies have generally found that caffeine produces acute rises in systolic and diastolic BP that are additive to any stress-induced increases. Synergistic effects which might pose a more serious risk are rarely found. Heart rate data are less consistent, possibly due to the different ways HR is measured. Tolerance to the cardiovascular effects of caffeine has reliably been reported; however, overnight abstinence may be sufficient to negate tolerance effects to most levels of caffeine ingestion in typical caffeine users. Though caffeine drinkers may exhibit acute increases in BP, the long-term effects appear to be minimal. However, persons at risk for hypertension may be more vulnerable to the BP effects of caffeine.

Distress Vocalizations in Infant Rats: What's All the Fuss About?

Ultrasonic vocalizations emitted by infant rodents are typically characterized as cries of distress. There are two contexts that are known to reliably elicit ultrasound production: extreme cold exposure and administration of clonidine, an

Maintenance of arterial pressure in infant rats during moderate and extreme thermal challenge

aL2 adrenoceptor agonist. Noting that these two contexts both entail pronounced decreases in cardiac rate, we have hypothesized that the vocalizations are acoustic by-products of a physiological maneuver, the abdominal compression reaction (ACR), that increases venous return to the heart when return is compromised. As a critical test of this hypothesis, we measured venous pressure near the right atrium in 15-day-old rats after clonidine administration. Consistent with the ACR hypothesis, emission of ultrasound was accompanied by large and reliable increases in venous pressure and, therefore, venous return. These results provide strong, direct support for the ACR hypothesis and, by doing so, underscore the potential pitfalls of anthropomorphic interpretations of the vocalizations of infant rats.

Role of the anteroventral third ventricle (AV3V) region of the rat brain in the pressor response to γ2-melanocyte-stimulating hormone (γ2-MSH)

It has recently been demonstrated in week-old rats that extreme cold challenges that lead to significant bodily cooling result in decreased cardiac rate. To determine whether pups are able to maintain arterial pressure in the face of decreasing cardiac rate in extreme cold, we measured blood pressure in unanesthetized week-old rats. Instrumented pups were thermally challenged and thermoregulatory and cardiovascular responses were monitored. Despite pronounced decreases in cardiac rate in the cold, pups were able to maintain mean arterial pressure (MAP), presumably by increasing peripheral resistance. At the lowest air temperature (17 degrees C) pups emitted ultrasonic vocalizations, and these emissions were accompanied by pulsatile increases in intraabdominal pressure (IAP) and MAP. We hypothesize that these pulsatile increases in IAP during extreme cooling reflect the use of the abdominal compression reaction to increase venous return during periods of diminished cardiac output.

Cardiovascular and sympathetic nervous system responses to an acute stressor in borderline hypertensive rats (BHR)

We have examined the role of the anteroventral third ventricle (AV3V) region of the forebrain on the pressor responses to intravenous injections of the pituitary pressor agent, gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) and the direct acting alpha 1-adrenergic agonist, phenylephrine in unanesthetized rats. Lesions of the AV3V region produce a parallel shift to the right in the dose response curve to gamma 2-MSH, with no effect on the pressor response to phenylephrine. The lesion had no effect on the heart rate response to either agent. These experiments indicate that the forebrain region surrounding the anterior third ventricle area is important to some of the cardiovascular actions of gamma 2-MSH.

The role of beta1 and beta2 adrenoceptors in isoproterenol-induced drinking

The present study examined cardiovascular and plasma catecholamine responses to acute footshock stress in adult male Wistar-Kyoto (WKY) normotensive, borderline hypertensive (BHR), and spontaneously hypertensive (SHR) rats. Basal mean arterial pressure and heart rate were equivalent for SHRs and BHRs, and levels for both groups were elevated compared to WKYs. Following transfer to the footshock chamber, blood pressure increased to a greater degree in SHRs than in WKYs or BHRs. However, the tachycardia was exaggerated in both BHRs and SHRs compared to WKYs. In response to intermittent footshock stress, all groups had comparable heart rate increases while maintaining blood pressure near baseline levels. SHRs demonstrated a sympathetic hyperresponsiveness to footshock stress, with greater increases in plasma norepinephrine and epinephrine levels than WKYs immediately following footshock. At 5 minutes postfootshock, plasma catecholamines remained elevated in SHRs over both WKYs and BHRs. Plasma catecholamine increases following footshock were comparable at all time points between WKYs and BHRs. The present results demonstrate that sympathetic responsiveness of BHRs to acute footshock stress is more similar to normotensive WKYs than to hypertensive SHRs.

Further evidence that BAT thermogenesis modulates cardiac rate in infant rats

The present study examined the contribution of beta1 and beta2 adrenoceptor activation to drinking behavior and the stimulation of plasma renin activity produced by the mixed beta adrenoceptor agonist, isoproterenol. The stimulation of drinking by beta adrenoceptor activation could occur via two independent pathways; by either directly stimulating renal beta1 adrenoceptors on the juxtaglomerular cells to release renin or by stimulating vascular beta2 adrenoceptors that would decrease blood pressure and activate afferent neural and humoral mechanisms. Selective pharmacological antagonism of each adrenoceptor type was achieved by administering atenolol (2.5 mg/kg), a beta1 adrenoceptor antagonist, or ICI 118,551 (1 mg/kg), a beta2 adrenoceptor antagonist, before treatment with isoproterenol (25 micrograms/kg). Neither adrenoceptor mechanism alone could account for all of the water intake or stimulation of plasma renin activity due to isoproterenol treatment. Cardiovascular recordings confirmed the selectivity of the antagonists to their respective receptor subtypes, with atenolol blocking the beta1 adrenoceptor-mediated heart rate increases and ICI 118,551 blocking the beta 2 adrenoceptor-mediated depressor response to isoproterenol. The results provide evidence that the stimulation of both beta1 and beta2 adrenoceptors by isoproterenol acts in a synergistic manner to induce drinking and renin-angiotensin system activation.

Dam strain affects cardiovascular reactivity to acute stress in BHR

Previous research in infant rats suggested that brown adipose tissue (BAT), by providing warm blood to the heart during moderate cold exposure, protects cardiac rate. This protective role for BAT thermogenesis was examined further in the present study. In experiment 1, 1-wk-old rats in a warm environment were pretreated with saline or chlorisondamine (a ganglionic blocker), and then BAT thermogenesis was stimulated by injection with the β3-agonist CL-316243. In experiment 2, pups were pretreated with chlorisondamine and injected with CL-316243, and after BAT thermogenesis was stimulated the interscapular region of the pups was cooled externally with a thermode. In both experiments, cardiac rate, oxygen consumption, and physiological temperatures were monitored. Activation of BAT thermogenesis substantially increased cardiac rate in saline- and chlorisondamine-treated pups, and focal cooling of the interscapular region was sufficient to lower cardiac rate. The results of these studies support the hypothesis that BAT thermogenesis contributes directly to the modulation of cardiac rate.Previous research in infant rats suggested that brown adipose tissue (BAT), by providing warm blood to the heart during moderate cold exposure, protects cardiac rate. This protective role for BAT thermogenesis was examined further in the present study. In experiment 1, 1-wk-old rats in a warm environment were pretreated with saline or chlorisondamine (a ganglionic blocker), and then BAT thermogenesis was stimulated by injection with the beta3-agonist CL-316243. In experiment 2, pups were pretreated with chlorisondamine and injected with CL-316243, and after BAT thermogenesis was stimulated the interscapular region of the pups was cooled externally with a thermode. In both experiments, cardiac rate, oxygen consumption, and physiological temperatures were monitored. Activation of BAT thermogenesis substantially increased cardiac rate in saline- and chlorisondamine-treated pups, and focal cooling of the interscapular region was sufficient to lower cardiac rate. The results of these studies support the hypothesis that BAT thermogenesis contributes directly to the modulation of cardiac rate.

Beta-2 Adrenoceptor Mediated Vasodilation: Role in Cardiovascular Responses to Acute Stressors in Spontaneously Hypertensive Rats

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.