Effect of transmural pressure on constrictor reactions of caudal artery in hypotensive and hypertensive rats.

Clipping of the abdominal aorta distally to the renal arteries produces a persistent decrease in blood pressure in hindquarter vessels by 35-40%. On week 6-7 postoperation, the reactions of the caudal artery perfused in vitro under constant pressure to norepinephrine were studied. At transmural pressure of 150 mm Hg, the vascular responses in hypotensive rats were reduced compared to those in normotensive control. By contrast, the responses of hypertensive vessels were more pronounced at 75 mm Hg even after deendothelization.

[Neurogenic contractions of the rat tail artery under isobaric conditions: effect of transmural pressure and function of the endothelium]. / Neirogennoe sokrashchenie khvostovoi arterii krysy v izobaricheskikh usloviiakh: vliianie transmural'nogo davleniia i éndoteliia.

In stimulation of the rat nerve with a modulated sine pattern, an increase in the modulating frequency from 0.03 to 0.15 Hz diminished the latency between the stimulating signals and changes in the vessel resistance as well as the amplitude of the flow oscillations, but did not affect tonic contractions of the vessel. A reduction of transmural pressure from 80 to 40 mm Hg increased both the tonic and the phasic components of the vessel contraction. Following the endothelium removal no change in the response latency occurred. The data obtained suggest that, during a rhythmic neurogenic influence, the vascular endothelium may work as an "amplifier" of the vessel's phasic contractions.

[Adaptation of resistance vessels to the transmural pressure level]. / Adaptatsiia rezistivnykh sosudov k urovniu transmural'nogo davleniia.

The transmural pressure level influences vascular structure and function. A short-term distension enhances sensitivity of the vascular smooth muscle to constrictor agonists. A long-term change in the blood pressure leads to structural autoregulation of arterial vessels. The resulting change of the wall thickness modifies performance of the distension-dependent mechanisms and alters thereby the pressure range in which the myogenic amplification of vasoconstriction is manifested.

Wall thickness and constrictive responses of the caudal artery in rats with renovascular hypertension.

In rats with hypertension modeled by the one kidney-one clamp method, constrictory responses of the isolated caudal artery to norepinephrine differed under various perfusion conditions. Vascular reactions in hypertensive rats were more potent at a constant flow rate, and less potent at a constant pressure compared to those in normotensive rats. Previous experiments demonstrated similar changes in constrictory responses of the caudal artery in spontaneously hypertensive rats. It is assumed that these peculiarities of the vascular reactivity during hypertension are determined by thickening of the smooth muscle layer of the vascular wall.

Frequency characteristics of blood pressure oscillations evoked by sympathetic transmitters, noradrenaline and adenosine triphosphate.

Mean arterial pressure (MAP) was recorded beat-to-beat in chronically instrumented, conscious, unrestrained rats under control conditions and after pharmacological inhibition of vascular sympathetic influences by means of: (1) ganglion blockade with chlorisondamine; (2) alpha-adrenoceptor antagonist phentolamine; (3) P2 receptor blockade with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). Angiotensin II was continuously infused to prevent drastic MAP decrease during chlorisondamine and phentolamine administration. Overall MAP variability increased after ganglion blockade and combined blockade of adreno- and purinoceptors. It increased also after inhibition of purinergic influences, but was not significantly changed after vascular adrenergic blockade. Spectral analysis of spontaneous MAP fluctuations in intact rats revealed a peak centered at 0.4-0.5 Hz. Ganglion blockade suppressed MAP fluctuations with frequencies from 0.1 to 0.8 Hz. After blockade of alpha-adrenoceptors, MAP spectral density was suppressed only within the 0.1-0.45-Hz band, but increased in the 0.45-0.8-Hz band. In the latter case, sympathetically-induced peak of MAP spectrum was centered on 0.6 Hz, being evoked, presumably, by adenosine triphosphate (ATP). Blockade of P2 receptors by PPADS enhanced MAP fluctuations in the 0.1-0.45-Hz frequency band, i.e. the noradrenaline-induced peak was centered on 0.2 Hz. No peaks were observed in the 0.1-0.8-Hz frequency band during combined blockade of adreno- and purinoceptors. The present study supports the concept that sympathetic purinergic co-transmission is essential for stabilization of MAP level. MAP fluctuations evoked by noradrenaline and ATP can be distinguished by their frequency characteristics.

An experimental study and mathematical simulation of adrenergic control of hindlimb vessels in rats after 3-week tail suspension.

Adrenoreactivity of rat hindlimb vessels was studied in experiments with constant-pressure saline perfusion. An original mathematical model was applied to evaluate the mechanism of changes in vascular tone regulation. A 3-week suspension resulted in decreased responses to sympathetic nerve stimulation, as well as to exogenous noradrenaline, the latter effect being registered when the pressure level was close to normal. Mathematical simulation indicated that long-term suspension induces both structural and functional changes in the vascular bed of the hind limbs, one of which is a disorder in the myogenic mechanisms of vascular tone regulation. In suspended rats, suppression of the myogenic response can be one of the reasons for decreased vessel reactivity to constrictor stimuli and, consequently, for disturbances in blood flow regulation in skeletal muscles of the hind limbs.

Responses to noradrenaline of tail arteries in hypertensive, hypotensive and normotensive rats under different regimens of perfusion: role of the myogenic response.

The vasoconstrictor effects of noradrenaline were studied in spontaneously hypertensive rats (SHR) compared with Wistar Kyoto rats (WKY), and in Wistar rats with regional hypotension (WH) compared to control Wistar rats (WC). The abdominal aorta was ligated in WH distal to the renal arteries, lowering blood pressure in the hindquarters by 41% and tail artery wall cross-sectional area by 35% compared with WC. A cylindrical segment was dissected from the proximal part of the tail artery, cannulated at both ends and perfused with Krebs-Henseleit solution either at constant flow starting from a pressure of 120 mmHg or at a constant pressure of 120 mmHg. The cumulative dose-response relationships for noradrenaline were determined in control conditions and subsequently in the presence of gadolinium (100 microM), a non-specific blocker of mechanosensitive channels. Under constant-flow perfusion noradrenaline evoked a more prominent resistance increase in SHR compared with WKY and in WC compared with WH. Similar relations were seen in the presence of gadolinium, although responses were reduced. At constant pressure perfusion the vasoconstrictor response to noradrenaline was lower in SHR compared with WKY and in WC compared with WH. Application of gadolinium under constant-pressure perfusion reduced responses in WKY and WH, so that vasoconstriction in SHR became more pronounced than that in WKY and in WC than that in WH. It is suggested that the results can be explained by the difference in wall thickness causing different degrees of activation of the myogenic response to distension.

The role of purinergic and adrenergic transmitters of the sympathetic system in the control of arterial blood pressure variability.

Variability of mean arterial pressure (MAP) was examined in chronically instrumented, conscious, freely moving rats with pharmacologically altered efferent sympathetic influences on the cardiovascular system. MAP was recorded for 30 min beat-to-beat, using a computer under both control and experimental conditions: after administration of adrenoceptor antagonists (prazosin or phentolamine) or under P2X receptor inactivation produced either by desensitization with alpha, beta-methylene ATP or by PPADS blockade. Inhibition of adrenergic sympathetic effects on the cardiovascular system produced long-lasting and stable decrease in MAP. Prazosin did not modify MAP variability whereas phentolamine enhanced it. Under P2X receptor desensitization MAP decreased, the hypotensive effect being accompanied by a significant increase in MAP variability. A similar increase in MAP variability was observed after PPADS administration, while MAP level was not changed. Administration of PPADS in combination with phentolamine increased MAP variability more significantly than each of the drugs given separately. Changes in MAP variability under the various experimental conditions were not consistently correlated with changes in heart rate variability. We propose that ATP, being a mediator of sympathetic vasoconstriction, participates in baroreceptor-induced stabilization of MAP level.

Effect of noradrenaline on tail arteries of SHR and WKY under perfusion at constant flow and constant pressure.

Vasoconstrictor effects of noradrenaline were compared in 6- to 7-month-old spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. A cylindrical segment was dissected from the proximal part of tail artery, cannulated at both ends and perfused alternately either at constant flow or constant pressure. Two series of experiments were performed. In the first series, vessels were perfused/superfused with Krebs-Henseleit solution. In the second one a modified salt solution was used, in which NaCl was totally replaced by an equimolar amount of KCI. Under constant flow conditions noradrenaline evoked a more prominent resistance increase in SHR compared with WKY independently of the composition of solution (normal or high-K+) used. At constant pressure perfusion with normal solution, the vasoconstrictor response to noradrenaline was more prominent in WKY. Under application of high-K+ solution, vasoconstriction at constant pressure in SHR became more pronounced than that in WKY. We suggest that there is greater wall thickness:lumen diameter ratio in SHR vessels and thus different contribution of distension-activated myogenic response is of primary importance for the data obtained.

[Attenuation of the efficacy of vasoconstrictive effects in rats after a 3-week suspension]. / Snizhenie éffektivnosti vazokonstriktornykh vliianii u krys posle 3-nedel'nogo vyveshivaniia.

Male Wistar rats were maintained suspended by the skin of posterior third of the back for three weeks. Constrictive reactions to norepinephrine and irritation of sympathetic nerves were studied with hindlimb vessels perfused with physiological solution at constant pressure. Perfusion pressure was stabilized at 40, 80, and 120 mmHg. During complete relaxation of the vascular smooth muscles the volumetric rate of perfusate flow in experimental animals was reduced comparing with their controls. This implies narrowing of the lumen in resistive vessels caused by suspension. Following suspension, reaction of rat's nerves to irritation was markedly lower than in the control at all levels of pressure. At 40 mmHg vessels of the suspended rats were more sensitive to norepinephrine; however, at 80 and 120 mmHg vascular sensitivity to the agent was reduced in the test group vs. the control. Suppression of the reactivity of hindlimb vessels to the constrictive agents may be one of the causes of failure of mechanisms of blood redistribution following prolonged gravitational deloading.

[The activation of blood-vessel smooth muscles increases the resistance to compression deformation]. / Aktivatsiia gladkikh myshts krovenosnogo sosuda uvelichivaet ego soprotivlenie deformatsii szhatiia.

In cylindric fragments of the rat tail arteries, activation of the smooth muscle with noradrenaline was found to enhance the vessels' rigidity both in stretching and in compression, i.e., the activation of the smooth muscle layer decreased the arteries' pliability.

[The effect of captopril on the arterial pressure, structural resistance and vascular reactivity of the kidney in rats with nephrogenic hypertension]. / Vliianie kaptoprila na arterial'noe davlenie, strukturnoe soprotivlenie i reaktivnost' sosudov pochi u krys s nefrogennoi gipertenziei.

The angiotensin-converting enzyme inhibiting agent captopryl suppressed a moderate hypertension in rats with pyelonephritis and with ureteral obstruction, but not in rats with ureteral obstruction combined with the renal artery constriction. The suppression of the hypertension was accompanied by a reversion of structural alterations in the blood vessels.

The role of purinergic neurotransmission in various cardiovascular reflexes.

In urethane-anaesthetized rats the effects of alpha-adrenoceptor antagonists and desensitization of P2-purinoceptors with alpha,beta-methylene ATP on the pressor reflex responses were investigated. Pressor responses were elicited by electrical stimulation of the central end of the sciatic nerve, by asphyxia and by occlusion of the common carotid artery. Responses to sciatic nerve stimulation and to asphyxia, but not those to carotid artery occlusion were entirely suppressed by dihydroergotamine and phentolamine. Under the action of dihydroergotamine the sinocarotid reflex decreased by over 70% in 40% of the experiments. In 60% of experiments the response was only slightly reduced or even augmented, but it was entirely inhibited by subsequent desensitization with alpha,beta-methylene ATP. The magnitude of response to sciatic nerve stimulation was almost unaffected by alpha,beta-methylene ATP, while the response to carotid occlusion was decreased by 40-50%. The recovery of purinoceptor sensitivity to alpha,beta-methylene ATP was accompanied by restoration of the sinocarotid reflex. It is suggested that purinergic neurotransmission plays a considerable role in the pressor sinocarotid reflex, while in the pressor response to stimulation of somatic afferents its role is negligible.

Vasoconstrictor reactions in spontaneously hypertensive rats versus Wistar Kyoto can be increased or decreased depending on the conditions of perfusion.

The reactions of resistance vessels in SHR and WKY hindquarters were compared during saline or blood perfusion. During saline constant-flow perfusion at all initial pressures (80-200 mmHg) sympathetic vasoconstrictor effects were greater in SHR than those in WKY. During perfusion at constant and equal pressure vasoconstrictor responses were greater in SHR vs. WKY only at high pressure--200 mmHg. On the other hand, under constant pressure conditions at lower pressures (80 and 120 mmHg) sympathetic stimulation induced weaker responses in SHR than in WKY, which at, for example, 80 mmHg was the case at every frequency of sympathetic stimulation used (2-20 Hz). Also, the responses to exogenous noradrenaline and vasopressin occurred during perfusion at low (80 mmHg) and for both equal constant-pressure conditions lower in SHR than in WKY. Comparison of sympathetic effects in SHR and WKY during blood hindquarter perfusion revealed similar results. Also, when SHR and WKY responses were compared at their ordinary levels of constant-pressure, sympathetic vasoconstrictor effects in SHR were lower than those in WKY.

Tone, autoregulatory properties, and wall thickness-to-radius ratio in skeletal muscle arterioles.

Internal diameter, wall thickness, wall thickness-to-radius ratio (W/r), and blood flow velocity in arterioles of different branching orders were measured in the rat cremaster muscle. The heterogeneity of W/r increased in more distal orders. During papaverine treatment, there was a direct correlation between vasodilation and W/r. When pressure was decreased by 20%, 42% of arterioles showed autoregulation; the remaining arterioles constricted in proportion to initial W/r. Similarly, the dilatation of arterioles with autoregulatory properties increased with initial W/r. It is concluded that W/r is an important parameter quantitatively related to tone, mechanical characteristics, and autoregulatory properties of arterioles.

[Changes in the systemic hemodynamics and the vascular bed of the skeletal muscles in rats adapted to hypoxia]. / Izmeneniia sistemnoi gemodinamiki i krovenosnogo rusla skeletnykh myshts u krys, adaptirovannykh k gipoksii.

In adult rats after 2 weeks of adaptation to simulated altitude cardiac output was increased by 22% and total peripheral resistance was decreased by the same value. The structural component of peripheral vascular resistance was decreased in rats which were trained 18-20 hrs during 2 weeks and in those trained daily for only 2 hrs. In hypoxically trained rats, the vessel reactivity to sympathetic stimulation was decreased, but to exogenous noradrenaline it was unchanged. Angiogenesis seems to be one of the mechanisms which increase the stability of oxygen transport in microcirculation.