American journal of physiology. Heart and circulatory physiology
-
Am. J. Physiol. Heart Circ. Physiol. · Jul 2010
Analysis of responses to the Rho-kinase inhibitor Y-27632 in the pulmonary and systemic vascular bed of the rat.
Responses to the Rho kinase inhibitor Y-27632 were investigated in the anesthetized rat. Under baseline conditions intravenous injections of Y-27632 decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressures were enhanced when baseline tone was increased with U-46619, and under elevated tone conditions Y-27632 produced similar percent decreases in pulmonary and systemic arterial pressures. ⋯ These data suggest that Rho kinase is involved in the regulation of baseline tone and in the mediation of pulmonary vasoconstrictor responses. The present data suggest that the hypoxic pulmonary vasoconstrictor response is modulated by the release of NO that mediates the nonsustained component of the response in the anesthetized rat. These data suggest that Rho kinase and NOS play important roles in the regulation of vasoconstrictor tone in physiological and pathophysiological states and that monocrotaline-induced pulmonary hypertension can be reversed by agents that inhibit Rho kinase, generate NO, or stimulate soluble guanylate cyclase.
-
Am. J. Physiol. Heart Circ. Physiol. · Jul 2010
Dynamic control of maximal ventricular elastance via the baroreflex and force-frequency relation in awake dogs before and after pacing-induced heart failure.
We investigated to what extent maximal ventricular elastance (E(max)) is dynamically controlled by the arterial baroreflex and force-frequency relation in conscious dogs and to what extent these mechanisms are attenuated after the induction of heart failure (HF). We mathematically analyzed spontaneous beat-to-beat hemodynamic variability. First, we estimated E(max) for each beat during a baseline period using the ventricular unstressed volume determined with the traditional multiple beat method during vena cava occlusion. ⋯ However, the ABP-->E(max) transfer function was more sluggish than the HR-->E(max) transfer function with overall time constants (indicator of full system response time to a sudden input change) of 11.2 +/- 2.8 and 1.7 +/- 0.5 s (P < 0.05), respectively. During the HF condition, the ABP-->E(max) and HR-->E(max) transfer functions were markedly depressed with gain values reduced to -0.0002 +/- 0.007 ml(-1) and -0.001 +/- 0.004 mmHg.ml(-1).(beats/min)(-1) (P < 0.1). E(max) is rapidly and significantly controlled at rest, but this modulation is virtually abolished in HF.
-
Am. J. Physiol. Heart Circ. Physiol. · Jun 2010
Akt1 genetic deficiency limits hypothermia cardioprotection following murine cardiac arrest.
Therapeutic hypothermia (TH) cardioprotection has recently been associated with increased Akt signaling in a rat model of cardiac arrest. However, it is not known whether Akt is required for this beneficial effect of TH. We used a mouse model of cardiac arrest demonstrating TH cardioprotection to study the response of mice deficient in an Akt1 allele. ⋯ TH-associated alterations in Akt phosphorylation, stroke volume, heart rate, and cardiac output were abrogated in Akt1(+/-) animals. In conclusion, TH improves post-ROSC cardiac function and increases Akt phosphorylation in WT, but not Akt1(+/-), mice. The Akt1 isoform appears necessary for TH-mediated cardioprotection.
-
Am. J. Physiol. Heart Circ. Physiol. · Jun 2010
The heart rate response to spontaneous arousal from sleep is reduced in children with Down syndrome referred for evaluation of sleep-disordered breathing.
Arousal from sleep in healthy adults is associated with a large, transient increase in heart rate (HR). Individuals with Down syndrome (DS) have attenuated cardiovascular responses to autonomic tests during wakefulness. We tested the hypothesis that the HR response to arousal from sleep is reduced in children with DS and obstructive sleep apnea (OSA) compared with healthy children. ⋯ Post hoc analysis revealed that HR in the DS group was significantly lower than both control groups at 1-4 s in NREM and at 4 to 5 s in REM (P < 0.05 for all). In conclusion, the HR response to spontaneous arousal from sleep is reduced in children with DS and OSA compared with healthy children. This attenuated cardiovascular response could be due to reduced sympathetic activation or blunted vagal withdrawal and may have implications for the child with DS and OSA.
-
Am. J. Physiol. Heart Circ. Physiol. · May 2010
Influence of breathing frequency on the pattern of respiratory sinus arrhythmia and blood pressure: old questions revisited.
Respiratory sinus arrhythmia (RSA) is classically described as a vagally mediated increase and decrease in heart rate concurrent with inspiration and expiration, respectively. However, although breathing frequency is known to alter this temporal relationship, the precise nature of this phase dependency and its relationship to blood pressure remains unclear. ⋯ The principal findings were 1) the time interval between R-R maximum and expiration onset remained the same ( approximately 2.5-3.0 s) irrespective of breathing frequency (P = 0.10), whereas R-R minimum progressively shifted from expiratory onset into midinspiration with slower breathing (P < 0.0001); 2) there is a clear qualitative distinction between pre- versus postinspiratory cardiac acceleration during slow (0.10 Hz) but not fast (0.20 Hz) breathing; 3) the time interval from inspiration onset to SBP minimum (P = 0.16) and from expiration onset to SBP maximum (P = 0.26) remained unchanged across breathing frequencies; 4) SBP maximum and R-R maximum maintained an unchanged temporal alignment of approximately 1.1 s irrespective of breathing frequency (P = 0.84), whereas the alignment between SBP minimum and R-R minimum was inconstant (P > 0.0001); and 5) beta(1)-adrenergic blockade did not influence the respiration-RSA relationships or distinct RSA patterns observed during slow breathing, suggesting that temporal dependencies associated with alterations in breathing frequency are unrelated to cardiac sympathetic modulation. Collectively, these results illustrate nonlinear respiration-RSA-blood pressure relationships that may yield new insights to the fundamental mechanism of RSA in humans.