A role for the central histaminergic system in the leptin-mediated increase in cardiovascular dynamics.

The central nervous system (CNS) histaminergic neurons have been shown to regulate feeding behavior and are a target of leptin in the brain. The present study aimed to examine the involvement of the histaminergic system in the leptin-mediated regulation of cardiovascular dynamics. We investigated the cardiovascular responses to the CNS administration of histamine, leptin and alpha-melanocyte stimulating hormone (alpha-MSH) both in the presence and absence of the histamine H1 antagonist, chlorpheniramine. The intracerebroventricular (i.c.v.) administration of histamine resulted in an immediate increase in both mean arterial pressure (MAP) and heart rate (HR) and vasoconstricted the iliac, renal and superior mesenteric vessels. The i.c.v. pretreatment with chlorpheniramine attenuated the histamine-induced increase in MAP, HR and decreased vascular conductance. The i.c.v. administration of leptin increased MAP and HR and decreased vascular conductance. The i.c.v. pretreatment with chlorpheniramine decreased the leptin-induced increase in MAP and the leptin-mediated iliac vasoconstriction. The i.c.v. administration of alpha-MSH also increased MAP, HR and decreased vascular conductance. However, pretreatment with chlorpheniramine did not influence the central alpha-MSH-mediated increase in MAP, HR and decreased vascular conductance. These results indicate that the central histaminergic system mediated by H1 receptors have a role in the central signaling pathway and is involved in leptin's regulation of cardiovascular dynamics. It appears that leptin directly or indirectly stimulates histaminergic neurons that lead to increased cardiovascular activity.

Cardiovascular responses to central administration of mu and kappa opioid receptor agonist and antagonist in normal rats.

The response to centrally administered beta-endorphin has been characterized by decreasing sympathetic nervous activity and decreased cardiovascular tone. We investigated the effect of the central administration of both mu and kappa opioid receptor agonist and antagonists on cardiovascular responses. The administration of the mu agonist, DAMGO (0.2nmol) increased the mean arterial pressure (MAP) and stimulated iliac vasoconstriction while higher doses (2 and 20nmol) decreased MAP and stimulated iliac vasodilation. The administration of the kappa receptor agonist, Dynorphin decreased the MAP and stimulated superior mesenteric vasodilation. beta-Funaltrexamine reduced MAP and superior mesenteric vasodilation while nor-binaltorphimine increased MAP and iliac and superior mesenteric vasoconstriction. We conclude that mu receptor activation decrease or increase MAP depending on the mu agonist concentration. However, kappa receptor activation is consistently associated with a decrease in MAP.

Insulin mediated hemodynamic responses in spontaneous hypertensive rats (SHRs): effect of chromosome 4 gene transfer.

The spontaneous hypertensive rat (SHR) is a widely studied model of essential hypertension and has been reported to exhibit alterations in carbohydrate and lipid metabolism. Genetic linkage studies implicated that SHR carries deletion variant of Cd36 gene of chromosome 4, the gene that encodes fatty acid transporter. Thus it could be possible that primary genetic defect in SHR is compromised tissue utilization of fatty acid that would form the basis for the pathogenesis of hyperinsulinemia, insulin resistance and insulin-mediated responses. We measured both the hemodynamic and metabolic responses to insulin in SHR in comparison with the chromosome congenic spontaneous hypertensive rats (cSHRs) (rats in which piece of chromosome 4 containing wild type Cd36 was integrated into the SHR genome). A bolus infusion of insulin increased iliac conductance and decreased blood pressure in Wistar Kyoto (WKY) rats. However, in SHR insulin did not reduce blood pressure as in WKY but after about 15 min it significantly enhanced blood pressure and reduced iliac conductance. Whereas in cSHR insulin did not reduce blood pressure as in WKY rats. However, pressor responses to insulin were eliminated by chromosome 4 gene transfer. Glucose clearance was significantly slower in both SHR and cSHR. Glucose tolerance test revealed that SHR are hyperinsulinemic and insulin resistant. These findings indicate that transfer of segment of chromosome 4 from Brown Norway rats onto spontaneous hypertensive background eliminates hyperinsulinemia and pressor effects of insulin.

Postexercise alpha-adrenergic receptor hyporesponsiveness in hypertensive rats is due to nitric oxide.

We tested the hypothesis that a single bout of dynamic exercise produces a postexercise hypotension (PEH) and alpha(1)-adrenergic receptor hyporesponsiveness in spontaneously hypertensive rats (SHR). The postexercise alpha(1)-adrenergic receptor hyporesponsiveness is due to an enhanced buffering of vasoconstriction by nitric oxide. Male (n = 8) and female (n = 5) SHR were instrumented with a Doppler ultrasonic flow probe around the femoral artery. Distal to the flow probe, a microrenathane catheter was inserted into a branch of the femoral artery for the infusion of the alpha(1)-adrenergic receptor agonist phenylephrine (PE). A microrenathane catheter was inserted into the descending aorta via the left common carotid artery for measurements of arterial pressure (AP) and heart rate. Dose-response curves to PE (3.8 x 10(-3) - 1.98 x 10(-2)microg/kHz) were generated before and after a single bout of dynamic exercise. Postexercise AP was reduced in male (13 +/- 3 mmHg) and female SHR (18 +/- 7 mmHg). Postexercise vasoconstrictor responses to PE were reduced in males due to an enhanced influence of nitric oxide. However, in females, postexercise vasoconstrictor responses to PE were not altered. Results suggest that nitric oxide- mediated alpha(1)-adrenergic receptor hyporesponsiveness contributes to PEH in male but not female SHR.

Collaborative testing enhances student learning.

Examinations and quizzes should be used as learning as well as assessment tools. To achieve this goal, an assessment procedure was developed to enhance as well as assess student learning. Students were tested on four different topics of cardiovascular physiology. Each topic was tested by a different type of quiz (fill in the blanks, single best response multiple choice, short essay, or true/false). The students first completed a quiz individually. Once the quiz was completed individually, the students completed the same quiz in groups. Eighty percent of the score on the quiz was based on the individual results, and 20% of the score on the quiz was based on the group results. The performance on the quizzes was significantly higher (P < 0.001) when students completed the quizzes in groups than when they completed the quizzes individually. Results document that completing the quizzes in groups enhances the understanding of the material. In addition, students rated this format superior to the traditional method.

Cardiovascular action of insulin-like growth factor-1 is not mediated by calcitonin gene-related peptide neurons.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator located in the peripheral nerves including the perivascular nerves. Previous studies in our laboratory determined that the vasodilatory action of insulin is mediated in part by CGRP-containing neurons. Since insulin-like growth factor-1 (IGF-1) and insulin share molecular and receptor structural similarity as well as functional similarity, we investigated the role of the CGRP-containing neurons in IGF-1-mediated vasodilation. Wistar rats were made CGRP deficient by treatment with capsaicin (50 mg/kg) 1-3 d after birth. Vehicle-treated controls and CGRP-deficient rats were maintained for 12 to 13 wk. At this time rats were fasted overnight, anesthetized with urethane and chloralose, and prepared for cardiovascular recordings. The basal mean arterial pressure (MAP) was higher in CGRP-deficient rats when compared with controls. The infusion of IGF-1 resulted in an equivalent decrease in MAP in both the CGRP-deficient and control rats. IGF-1 infusion did not change the heart rate in control rats but decreased it in CGRP-deficient rats. IGF-1 also increased flow as determined by conductance in the iliac, renal, and superior mesenteric vascular beds in both vehicle controls and CGRP-deficient rats. We concluded that unlike insulin the IGF-1-mediated vasodilatory response is not mediated by the CGRP-dependent perivascular neurons.