Capacitance Vessels Research Articles

Different mechanisms between thromboxane A 2- and leukotriene D 4-induced nasal blockage in guinea pigs

Although thromboxane (TX)A 2 is involved in allergic rhinitis, the mechanisms inducing nasal blockage have not been elucidated. We evaluated the roles of nasal mucosal vascular changes following intranasal instillation of the TXA 2 analog U-46619 or leukotriene (LT)D 4 to induce nasal blockage in a guinea pig model of allergic rhinitis. Both U-46619- and LTD 4-induced nasal blockages in sensitized animals were swiftly and completely suppressed by a vasoconstrictor, naphazoline. The nitric oxide synthase inhibitor N ω-nitro- l-arginine methyl ester relieved LTD 4-induced nasal blockage, but not U-46619-induced nasal blockage. Although both agonists produced vasodilatation of nasal mucosa in vivo, LTD 4 caused vasodilatation while U-46619 caused vasoconstriction in vitro. Both LTD 4- and U-46619-induced nasal blockages in vivo should depend on vasodilatation of nasal mucosa. LTD 4-induced nasal blockage is induced by direct vasodilatation via nitric oxide. In contrast, U-46619-induced nasal blockage may be associated with contraction of a certain vein that should exist at the exit of capacitance vessels, leading to congestion of the nasal mucosa.

Effect of intermedin/adrenomedullin-2 on venous tone in conscious rats

We investigated the effect of intermedin/adrenomedullin-2 (3 and 10 nmol/kg, i.v.), a member of the calcitonin gene-related peptide family, relative to the vehicle (0.9% NaCl) on mean circulatory filling pressure (index of venous tone) in conscious rats: intact (unblocked) or ganglionic blocked through treatment with mecamylamine (10 mg/kg, i.v.) and noradrenaline (4 microg/kg/min, i.v.). In intact rats, both doses of intermedin/adrenomedullin-2 reduced mean arterial pressure (-14+/-3, -30+/-3 mmHg), but did not alter mean circulatory filling pressure; the high dose also increased heart rate. In ganglionic-blocked rats, both doses decreased mean arterial pressure (-22+/-3, -46+/-5 mmHg) and the high dose also decreased mean circulatory filling pressure (-2.81+/-0.82 mmHg), but neither dose affected heart rate. The vehicle did not have any effects in any of the groups. In addition, intermedin/adrenomedullin-2 did not have any effect on blood volume in both intact and ganglion-blocked rats. The results show that intermedin/adrenomedullin-2 is a dilator of arterial resistance and capacitance vessels.

α2-adrenoceptor agonists as nasal decongestants

Nasal congestion, one of the major disease features of rhinitis, is induced by the filling of venous sinusoids causing mucosal engorgement with resultant obstruction of nasal airflow. The only available drugs that directly target the underlying vascular features driving nasal obstruction are the sympathomimetic α-adrenoceptor agonists due to their vasoconstrictor action. However, standard decongestants are nonselective α-adrenoceptor agonists, which have the potential for side-effects liabilities such as hypertension, stroke, insomnia and nervousness. In the present study, the effects of nonsubtype selective α 2-adrenoceptor agonists BHT-920 and PGE-6201204 were evaluated in several isolated nasal mucosa contractile bioassays including dog, pig and monkey, and in a real-time tissue contractility assay using isolated pig nasal explants for BHT-920. The decongestant activity of PGE-6201204 was evaluated in vivo in a cat model of experimental congestion. Our results showed that α 2-adrenoceptor agonists (1) contract nasal mucosa of different species, (2) exert a preferential vasoconstrictor effect on the capacitance vessels (veins and sinusoids), and (3) elicit decongestion. In conclusion, a selective α 2-adrenoceptor agonist causing constriction preferentially in the large venous sinusoids and veins of nasal mucosa and producing nasal decongestion is expected to show efficacy in the treatment of nasal congestion without the characteristic arterio-constrictor action of the standard nonselective sympathomimetic decongestants.

Haemodynamics and wall remodelling of a growing cerebral aneurysm: A computational model

We have developed a computational simulation model for investigating an often postulated hypothesis connected with aneurysm growth. This hypothesis involves a combination of two parallel and interconnected mechanisms: according to the first mechanism, an endothelium-originating and wall shear stress-driven apoptotic behavior of smooth muscle cells, leading to loss of vascular tone is believed to be important to the aneurysm behavior. Vascular tone refers to the degree of constriction experienced by a blood vessel relative to its maximally dilated state. All resistance and capacitance vessels under basal conditions exhibit some degree of smooth muscle contraction that determines the diameter, and hence tone, of the vessel. The second mechanism is connected to the arterial wall remodeling. Remodeling of the arterial wall under constant tension is a biomechanical process of rupture, degradation and reconstruction of the medial elastin and collagen fibers. In order to investigate these two mechanisms within a computationally tractable framework, we devise mechanical analogues that involve three-dimensional haemodynamics, yielding estimates of the wall shear stress and pressure fields and a quasi-steady approach for the apoptosis and remodeling of the wall. These analogues are guided by experimental information for the connection of stimuli to responses at a cellular level, properly averaged over volumes or surfaces. The model predicts aneurysm growth and can attribute specific roles to the two mechanisms involved: the smooth muscle cell-related loss of tone is important to the initiation of aneurysm growth, but cannot account alone for the formation of fully grown sacks; the fiber-related remodeling is pivotal for the latter.

Can KAATSU be used for an orthostatic stress in astronauts?: A case study

The application of an orthostatic stress such as lower body negative pressure (LBNP) during exercise has been proposed to minimize the effects of weightlessness on the cardiovascular system and subsequently to reduce the cardiovascular deconditioning. The KAATSU training is a novel method for strength training to induce muscle strength and hypertrophy. KAATSU induces venous pooling of blood in capacitance vessels by restricting venous blood flow. Therefore, to investigate whether KAATSU can be used as an orthostatic stress, we examined the effects of KAATSU on the hemodynamic, autonomic nervous and hormonal parameters in one subject. The several parameters were measured by impedance cardiography; heart rate (HR), mean blood pressure (mBP), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), and heart rate variability (HRV). These data were obtained before (pre), during and after (post) pressurization (50 and 200 mmHg) on both thighs with KAATSU mini belts, and compared with those in standing. The serum concentration of noradrenaline (NA) and vasopressin (ADH), and plasma rennin activity (PRA) were also measured. The application of 200 mmHg KAATSU decreased SV, which was almost equal to the value in standing. HR and TPR increased in a similar manner as standing with slight change of mBP. High frequency (HFRR), a marker of parasympathetic nervous activity, decreased during both 200 mmHg KAATSU and standing, while LFRR/HFRR, a quantitative marker of sympathetic nervous activity, increased significantly. During KAATSU and standing, NA, PRA and ADH increased. These results indicate that the application of KAATSU on both thighs simulates systemic cardiovascular effects of orthostasis in one gravity (1G), and that KAATSU training appears to be a useful method for potential countermeasure like lower body negative pressure (LBNP) against orthostatic intolerance in space flight as well as strength training to induce muscle strength and hypertrophy.

Sleep, breathing and the nose

During sleep there is a discrete fall in minute ventilation and an associated increase in upper airway resistance. In normal subjects, the nasal part of the upper airway contributes only little to the elevation of the total resistance, which is mainly the consequence of pharyngeal narrowing. Yet, swelling of the nasal mucosa due to congestion of the submucosal capacitance vessels may significantly affect nasal airflow. In many healthy subjects an alternating pattern of congestion and decongestion of the nasal passages is observed. Some individuals demonstrate congestion of the ipsilateral half of the nasal cavity when lying down on the side. Nasal diseases, including structural anomalies and various forms of rhinitis, tend to increase nasal resistance, which typically impairs breathing via the nasal route in recumbency and during sleep. A role of nasal obstruction in the pathogenesis of sleep-disordered breathing has been implicated by many authors. While it proves difficult to show a relationship between the degree of nasal obstruction and the number of disturbed breathing events, the presence of nasal obstruction will most likely have an impact on the severity of sleep-disordered breathing. Identification of nasal obstruction is important in the diagnostic work-up of patients suffering from snoring and sleep apnea.

Angiotensin type-2 receptors and cardiovascular function: are angiotensin type-2 receptors protective?

The renin-angiotensin system is a coordinated hormonal cascade of critical importance to the regulation of blood pressure and cardiovascular function. The major effector peptide, angiotensin II, binds to two major receptors, angiotensin type-1 and angiotensin type-2. Most of the actions of angiotensin II are mediated by the angiotensin type-1 receptor, but recent evidence strongly suggests that the angiotensin type-2 receptor opposes the angiotensin type-1 receptor, particularly by promoting vasodilatation instead of vasoconstriction. Conclusive evidence has been presented indicating that the angiotensin type-2 receptor mediates vasodilatation in small resistance arterioles as well as in the coronary microcirculation. Substantial evidence also is available that the angiotensin type-2 receptor dilates large capacitance vessels, including the aorta, subjected to pressure-overload. The angiotensin type-2 receptor has recently been found to inhibit renin biosynthesis and secretion similar to the action of the angiotensin type-1 receptor. The angiotensin type-2 receptor appears to be cardioprotective, particularly in limiting cardiac remodeling following ischemic injury. The angiotensin type-2 receptor represents an important area of cardiovascular investigation with potential therapeutic implications for cardiac disease and hypertension.

Neurocardiogenic Syncope and Related Disorders of Orthostatic Intolerance

Received September 14, 2004; revision received January 31, 2005; accepted March 9, 2005. “We shall not cease from exploration and the end of all our exploring will be to arrive where we started and know the place for the first time” — —T.S. Eliot, Four Quartets Syncope, defined as transient loss of consciousness and postural tone with spontaneous recovery, has both challenged and perplexed physicians since the dawn of recorded time. The earliest written accounts come from Hippocrates, and the word syncope itself is derived from an old Greek term meaning “to cut short” or “interrupt.” Recurrent episodes of syncope may result from a large number of different disorders, all of which cause a transitory reduction in cerebral blood flow sufficient to disturb the normal functions of the brain. Over the last 2 decades, considerable attention has been given to types of syncope that occur due to a centrally mediated (or “reflex”) fall in systemic blood pressure, a condition that has been referred to as vasovagal (and later neurocardiogenic) syncope. However, research into the nature of this disorder revealed that it is but one aspect of a broad and varied group of disturbances in the normal functioning of the autonomic nervous system (ANS), each of which may result in orthostatic intolerance, hypotension, and ultimately syncope. Continued investigations into the nature of these similar yet different disorders has led to the development of a system of classification that attempts to more accurately reflect our understanding of these conditions and their interrelationships.1 The present system of classification has proven both functional and clinically relevant and includes a group of disorders that most investigators have thought to be principally autonomic in nature. Because both the cardiologist and the cardiac electrophysiologist frequently are expected to both diagnose and treat these conditions, the following …

Baroreflex mediated control of heart rate and vascular capacitance in trout

The baroreflex was triggered by altering branchial blood pressure with pre- and post-branchial occlusions for 30 s in rainbow trout Oncorhynchus mykiss. The cardiac limb of the baroreflex was monitored by continuous heart rate (f(H)) measurements. Responses of venous capacitance vessels were assessed, immediately following either occlusion, by measuring mean circulatory filling pressure (MCFP). Arterial responses were evaluated as the change in dorsal aortic blood pressure (P(da)) before and after pre-branchial occlusion. In untreated fish pre-branchial occlusion resulted in tachycardia (62.4+/-2.4 to 69.1+/-1.7 beats min(-1)), decreased venous capacitance reflected as an increase in MCFP (0.17+/-0.03 to 0.27+/-0.03 kPa) and increased P(da) (4.0+/-0.2 kPa compared to 3.2+/-0.1 kPa before occlusion). Post-branchial occlusion somewhat reversed the responses since f(H) decreased (62.4+/-2.4 to 53.0+/-3.1 beats min(-1)), whereas MCFP remained unaltered. Treatment with the alpha-adrenergic blocker prazosin (1 mg kg(-1)) increased resting MCFP to 0.33+/-0.03 kPa and appeared to abolish both venous and arterial responses to branchial occlusion. Subsequent atropine treatment (1.2 mg kg(-1)) abolished all chronotropic responses. We present for the first time ample evidence for baroreflex-mediated control of cardiovascular homeostasis, including both the chronotropic and the vascular limb of the baroreflex in an unanaesthetized fish. Furthermore, a novel technique to cannulate and occlude the dorsal aorta, using a Fogarty thru-lumen embolectomy catheter, is explained.

Cardiovascular and Renal Regulation by the Angiotensin Type 2 Receptor

The renin-angiotensin system is a coordinated hormonal cascade of major importance in cardiovascular and renal regulation. The principle effector of this system is the octapeptide angiotensin II (Ang II), which acts at 2 cell membrane receptors, AT1 and AT2. The majority of the actions of Ang II have been demonstrated to be mediated by the AT1 receptor, including growth promotion, vasoconstriction, antinatriuresis, aldosterone secretion, salt appetite, thirst, sympathetic outflow and inhibition of renin biosynthesis, and secretion.1 The AT2 receptor has been less well understood. Past studies, however, clearly demonstrated that the AT2 receptor mediates cellular differentiation and growth, opposing the actions of Ang II through the AT1 receptor.2 Studies in the mid to late 1990s demonstrated that AT2 receptor stimulation engenders an autacoid vasodilator cascade composed of bradykinin (BK), nitric oxide (NO), and guanosine cyclic 3′, 5′-monophosphate (cGMP).3–5 This discovery turned attention to the possibility that the AT2 receptor may mediate vasodilation, opposing the vasoconstrictor actions of Ang II at the AT1 receptor.6 Parallel cell signaling studies indicated that the AT2 receptor is G-protein–coupled (through Giα) and that receptor stimulation is accompanied by an increase in phosphotyrosine phosphatase activity and an inhibition of MAP kinase enzymes (p42 and p44) composing the extracellular signal-related kinase (ERK1/2). AT2 receptor-mediated inhibition of the extracellular signal-regulated kinase pathway opposed the actions of Ang II, resulting in extracellular signal-regulated kinase phosphorylation via the AT1 receptor.1,2,6,7 Work during the late 1990s through 2002 suggested that the AT2 receptor might serve as a vasodilator counterforce to the AT1 receptor.2,6,7 However, vasorelaxation was difficult to elicit in some experimental models, attributed to the relatively low level of AT2 receptor vascular expression compared with that of the …

Orale Antihistaminika der 2. Generation bei allergischer Rhinitis

Histamine is a key mediator of the allergic immediate reaction. Antihistamines belong to the most frequently used treatment modalities in allergic rhinitis. The National Libraray of Medicine was searched for current data of the effects of histamine and antihistamines in allergic rhinitis. Histamine acts on 4 different histamine receptors. Activation of H1-receptors on nasal trigeminal nerve fibers transmits nasal itch and sneezing. Nasal hypersecretion is mainly mediated by an trigeminal-parasympathetic reflex. Activation of H1-receptors results in contraction of nasal endothelial cells with consecutive plasma extravasation and edema formation. Histamine also activates H2-receptors on smooth muscle cells surrounding nasal capacitance vessels. They transmit muscle relaxation, increased blood content and an enlarged volume of nasal mucosa. Via peripheral H3-receptors, histamine modulates neurogenic inflammation and via H4-receptors functions of immune cells. Oral second generation antihistamines inhibit histamine dependent activation of nasal H1-receptors. They mainly reduce nasal itch, sneezing, and hypersecretion. In addition, allergy related activity impairment is reduced resulting in improved physical and mental performance. Second generation antihistamines reduce proinflammatory effects mediated by H1-receptors, however, drug concentrations necessary for mast cell stabilization as observed in vitro are not reached in vivo. Oral second generation antihistamines are readily absorbed and reduce allergy symptoms for approximately 24 hours, allowing convenient once daily medication. Modern antihistamines are generally safe; tachyphylaxis, tolerance or rebound has not been observed. Due to their minimal adverse effects and efficient symptom reduction oral second generation antihistamines are particularly useful for the treatment of less severe intermittent forms of nasal allergy.

Direct observation of epicardial coronary capillary hemodynamics during reactive hyperemia and during adenosine administration by intravital video microscopy.

Using high-resolution intravital charge-coupled device video microscopy, we visualized the epicardial capillary network of the beating canine heart in vivo to elucidate its functional role under control conditions, during reactive hyperemia (RH), and during intracoronary adenosine administration. The pencil-lens video-microscope probe was placed over capillaries fed by the left anterior descending artery in atrioventricular-blocked hearts of open-chest, anesthetized dogs paced at 60-90 beats/min (n = 17). In individual capillaries under control conditions, red blood cell flow was predominant during systole or diastole, indicating that the watershed between diastolic arterial and systolic venous flows is located within the capillaries. Capillary flow increased during RH and reached a peak flow velocity (2.1 +/- 0.6 mm/s), twice as high as control (1.2 +/- 0.5 mm/s), with enhancement of intercapillary cross-connection flow and enlargement of diameter (by 17%). With adenosine, capillary flow velocity significantly increased (1.8 +/- 0.7 mm/s). However, the increase in volumetric capillary flow with adenosine estimated from red blood cell velocity and diameter was less than the increase in arterial flow, whereas that during RH was nearly equivalent to the increase in arterial flow. There was a time lag of approximately 1.5 s for refilling of capillaries during RH, indicating their function as capacitance vessels. In conclusion, the coronary capillary network functions as 1) the major watershed between diastolic-dominant arterial and systolic-dominant venous flows, 2) a capacitor, and 3) a significant local flow amplifier and homogenizer of blood supply during RH, but with adenosine the increase in capillary flow velocity was less than the increase in arterial flow.

Endothelial venodilator response in carriers of genetic polymorphisms involved in NO synthesis and degradation.

Polymorphisms of the NOSIII gene and of the CYBA gene have been associated with a number of pathological conditions such as arterial hypertension, coronary artery disease, and myocardial infarction. Because endothelium-dependent vasodilation is impaired in these disorders, we hypothesized that polymorphisms of NOSIII or CYBA might modulate endothelial function of venous capacitance vessels already before cardiovascular disease becomes overt. Endothelium-dependent and -independent venodilation was assessed by measuring local vascular responses to bradykinin and sodium nitroprusside in the dorsal hand vein after preconstriction with phenylephrine in 72 healthy male Caucasians after careful exclusion of cardiovascular risk factors. Genotyping was performed for polymorphisms of the NOSIII gene (T-786C, G894T, (CA)(n)) and the CYBA gene (C242T). Genotype distribution for each polymorphism followed the Hardy-Weinberg equilibrium. In all studied single nucleotide polymorphisms no significant difference between the respective genotypes and the venodilator response to either sodium nitroprusside or bradykinin was observed, and the number of CA repeat copies was not related to the venodilator response to bradykinin. Mean venodilation induced by bradykinin 50 ng min(-1) (+/-SEM) for homozygote carriers of the single nucleotide polymorphisms was 48.9 +/- 8.5% venodilation (G894T; wild type: 49.8 +/- 6.9), 50.3 +/- 11.0% venodilation (T-786C; wild type: 42.6 +/- 5.2), and 30.4 +/- 9.1% venodilation (C242T; wild type: 49.2 +/- 6.0), respectively. This study suggests that the studied polymorphisms of NOSIII and CYBA do not significantly modulate endothelium-dependent venodilation in individuals without vascular risk factors.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Dynamic changes in expression of myosin phosphatase in a model of portal hypertension.

Myosin phosphatase is a target for signaling pathways that modulate calcium sensitivity of force production in smooth muscle. Myosin phosphatase targeting subunit 1 (MYPT1) isoforms are generated by cassette-type alternative splicing of exons in the central and 3' portion of the transcript. Exclusion of the 3' alternative exon, coding for the leucine zipper (LZ)-positive MYPT1 isoform, is associated with the ability to desensitize to calcium (relax) in response to NO/cGMP-dependent signaling. We examined expression of MYPT1 isoforms and smooth muscle phenotype in normal rat vessels and in a prehepatic model of portal hypertension characterized by arteriolar dilation. The large capacitance vessels, aorta, pulmonary artery, and inferior vena cava expressed predominantly the 3' exon-out/LZ-positive MYPT1 isoform. The first-order mesenteric resistance artery (MA1) and portal vein (PV) expressed severalfold higher levels of MYPT1 with predominance of the 3' exon-included/LZ-negative isoform. There was minor variation in the presence of the MYPT1 central alternative exons. Myosin heavy and light chain splice variants in part cosegregated with MYPT1 isoforms. In response to portal hypertension induced by PV ligature, abundance of MYPT1 in PV and MA1 was significantly reduced and switched to the LZ-positive isoform. These changes were evident within 1 day of PV ligature and were maintained for up to 10 days before reverting to control values at day 14. Alteration of MYPT1 expression was part of a complex change in protein expression that can be generalized as a modulation from a phasic (fast) to a tonic (slow) contractile phenotype. Implications of vascular smooth muscle phenotypic diversity and reversible phenotypic modulation in portal hypertension with regards to regulation of blood flow are discussed.

Influence of dietary salt intake on the response of isolated perfused mesenteric veins of the dog to vasoactive agents

BackgroundPrevious work has established that a high dietary salt intake results in enhanced arterial vasoconstrictor responses to stimulation with agonists. This investigation was designed to investigate the effects of dietary salt on the responses of isolated capacitance vessels (third order mesenteric veins). MethodsDogs were fed diets containing low, intermediate, and high levels of dietary salt (0.4, 3.0, and 6.0 mmol kg/day). The animals were killed, and lengths of mesenteric vein were mounted in a perfusion myograph with changes in lumenal diameter measured using a video tracking device. Responses to cumulative doses of norepinephrine (NE) and acetylcholine (Ach) were then determined. ResultsThe vasoconstrictor responses to NE were greater in the veins from dogs on a high salt diet. Acetylcholine also caused venoconstriction that also was greater in the high salt group of animals. Responses to Ach were unaffected by Nω-nitro-L-arginine methyl ester but were abolished by atropine. ConclusionsThese results indicate that mesenteric veins from dogs fed a high salt diet constrict more powerfully in response to agonists, which could contribute to the hypertensive effects of high intakes of dietary salt.

Dynamic changes in three-dimensional architecture and vascular volume of transmural coronary microvasculature between diastolic- and systolic-arrested rat hearts.

The phase difference of coronary arterial and venous flows indicates the importance of intramyocardial capacitance vessels in storing diastolic flow and in discharging volume in systole. However, the anatomic and functional characteristics of the capacitance vessels are unclear. We aimed to clarify those characteristics with their transmural difference by 3D visualization of transmural microvessels under diastole and systole. We performed complete intracoronary filling of a contrast medium into Langendorff's Wistar rat hearts under (1) St Thomas-perfused diastolic arrest (D-mode) and (2) BaCl(2)-induced systolic arrest (S-mode). Precise transmural 3D architectures of capillaries and of pre- and post-capillary microvessels (ie, microvessels larger than capillaries) were visualized clearly with a confocal laser scanning microscope and x-ray microcomputed tomography (microCT), respectively. Vascular volume fraction (VF) and systolic-induced VF reduction rate from D- to S-mode were analyzed. The net capillary VF in D-mode (20.4 +/- 0.9%) was 10 times that of larger microvessels and was reduced in S-mode by 32% without capillary collapse. Systolic-induced VF reduction rate was smaller in capillaries than in larger microvessels (48%; P<0.05). The larger microvessel VF in D-mode (2.2 +/-0.2%) was reduced in S-mode, accompanied by complicated 3D deformation. Capillaries were relatively resistant to the systolic extravascular compression compared with pre- and post-capillary microvessels, conveniently beneficial for the myocardial oxygen delivery throughout a cardiac cycle. Nevertheless, a larger change in the absolute volume of capillaries may function as effective capacitance. On one hand, the pre- and post-capillary microvessels showed a larger phasic change in resistance, which may function to maintain the capillary patency during systole.

Venodilator action of an organotransition-metal nitrosyl complex

Nitrovasodilators, such as nitroglycerin, cause endothelium-independent dilatation of arterial and capacitance vessels via the release of nitric oxide (NO). This study examined the venodilator effect of CpCr(NO) 2Cl (organotransition-metal nitrosyl complex) relative to that of nitroglycerin in conscious, unrestrained rats. Organotransition-metal nitrosyl complexes have releasable NO directly attached to metal centres. The dose–response effects of CpCr(NO) 2Cl and nitroglycerin on the mean arterial pressure and the mean circulatory filling pressure (index of the body venous tone) were obtained in rats continuously infused with either normal saline or noradrenaline. The results show that both CpCr(NO) 2Cl and nitroglycerin reduced the mean arterial pressure in rats with normal or elevated vasomotor tone. However, maximum depressor response of CpCr(NO) 2Cl was greater than that of nitroglycerin. In vehicle-treated rats, both compounds increased the mean circulatory filling pressure. In rats with elevated vasomotor tone through the infusion of noradrenaline, both agents reduced the mean circulatory filling pressure. These results show that CpCr(NO) 2Cl is an efficacious depressor and venodilator agent.

Role of short-term regulatory mechanisms on pressure response to hemodialysis-induced hypovolemia

A large inter-subject variability exists in the arterial pressure response to hemodialysis-induced blood volume (BV) withdrawal. We investigated the hypothesis that this variability is due to the inter-subject differences in the short-term reflex capacity to compensate for hypovolemia. Mean arterial pressure (MAP), heart rate (HR) and the percentage reduction in BV (%R-BV) were recorded in 32 subjects during their regular hemodialysis sessions. On the basis of absolute MAP changes between the beginning and the end of the session with respect to %R-BV at the end of the session, three distinct pressure responses were identified: (1) hypotension-prone response; (2) unstable response with delayed hypotension; and (3) hypotension-resistant response. For each kind of response, one patient was selected and a computer model of the cardiovascular system including the main short-term reflex compensatory mechanisms was used to analyze data collected over five consecutive sessions. The %R-BV and HR were used as model inputs, while simulated arterial pressure was fitted to the measured MAP by the tuning model parameters representing the efficiency in the control of venous capacity, microvascular resistance and heart inotropism. The model-based analysis related the hypotension-prone response to a lack of efficacy in capacity and resistance regulation. In the unstable response with delayed hypotension, the control of venous capacity was not effective and resistance control alone kept the pressure stable only for a limited %R-BV reduction (<5%). In the hypotension-resistant response, an efficient compensation of capacitance vessels was evidenced, and the slightly increasing arterial pressure was referred to a prevalence of cardiopulmonary pathway in the compensatory process. The model ascribes differences in pressure response to differences in the effectiveness of reflex compensatory mechanisms.

MECHANICAL CHARACTERISTICS OF CORONARY CIRCULATION

The phase opposition of velocity waveforms between coronary arteries (predominantly diastolic) and veins (systolic) is the most prominent characteristic of coronary hemodynamics. The phase opposition indicates the importance of intramyocardial capacitance vessels, as a determinant of phasic coronary arterial and venous flows. To investigate the functional characteristics of the intramyocardial capacitance vessels and its physiological significance, we analyzed the change in venous flow following changes in coronary arterial inflow. It was shown that during diastole the intramyocardial capacitance vessels have two functional components, unstressed volume and ordinary capacitance. Unstressed volume is defined as the volume of blood in a vessel at zero transmural pressure, and it was ~5% of the volume of the myocardium. The systolic coronary venous outflow showed a significant, positive correlation with the total displaceable blood volume stored in the intramyocardial unstressed volume and ordinary capacitance. When the unstressed volume was saturated, the coronary inflow was decreased significantly, compared with that for the unsaturated condition. Thus, the increase in intramyocardial blood volume decreases the coronary arterial inflow, whereas it enhances coronary venous outflow. The latter is an interesting analogy to the Starling's law of the heart.