a1_Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension – salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development. Our attention was focused on some cellular aspects (cell membrane function, ion transport, cell calcium handling), intra- and extrarenal factors affecting renal function and/or renal injury, local and systemic effects of reninangiotensin-aldosterone system, endothelial and smooth muscle changes responsible for abnormal vascular contraction or relaxation, altered balance between various vasoconstrictor and vasodilator systems in blood pressure maintenance as well as on the central nervous and peripheral mechanisms involved in the regulation of circulatory homeostasis. We also searched for the age-dependent impact of environmental and pharmacological interventions, which modify the development of high blood pressure and/or organ damage, if they influence the saltsensitive organism in particular critical periods of development (developmental windows). Thus, severe self-sustaining salt hypertension in young Dahl rats is characterized by pronounced dysbalance between augmented sympathetic hyperactivity and relative nitric oxide deficiency, attenuated baroreflex as well as by a major increase of residual blood pressure indicating profound remodeling of resistance vessels. Salt hypertension development in young but not in adult Dahl rats can be attenuated by preventive increase of potassium or calcium intake., a2_On the contrary, moderate salt hypertension in adult Dahl rats is attenuated by superoxide scavenging or endothelin-A receptor blockade which do not affect salt hypertension development in young animals., J. Zicha, ... [et al.]., and Obsahuje seznam literatury
Blood pressure (BP) level results from the balance of vasoconstrictors (mainly sympathetic nervous system) and vasodilators (predominantly nitric oxide and endothelium-derived hyperpolarizing factor). Most of the forms of experimental hypertension are associated with sympathetic hyperactivity and endothelial dysfunction. It is evident that nitric oxide and norepinephrine are antagonists in the control of calcium influx through L-type voltage-dependent calcium channels (L-VDCC). Their effects on L-VDCC are mediated by cGMP and cAMP, respectively. Nevertheless, it remains to determine whether these cyclic nucleotides have direct effects on L-VDCC or they act through a modulation of calcium-activated K+ and Cl- channels which influence membrane potential. Rats with genetic or salt hypertension are characterized by a relative (but not absolute) NO deficiency compared to the absolute enhancement of sympathetic vasoconstriction. This dysbalance of vasoconstrictor and vasodilator systems in hypertensive animals is reflected by greater calcium influx through L-VDCC susceptible to the inhibition by nifedipine. However, when the modulatory influence of cyclic nucleotides is largely attenuated by simultaneous ganglionic blockade and NO synthase inhibition, BP of spontaneously hypertensive rats remains still elevated compared to normotensive rats due to augmented nifedipine-sensitive BP component. It remains to determine why calcium influx through L-VDCC of hypertensive rats is augmented even in the absence of modulatory influence of major vasoactive systems (sympathetic nervous system, nitric oxide)., M. Pintérová ... [et al.]., and Obsahuje seznam literatury
High blood pressure (BP) of spontaneously hypertensive rats (SHR) is maintained by enhanced activity of sympathetic nervous system (SNS), whereas that of Ren-2 transgenic rats (Ren-2 TGR) by increased activity of renin-angiotensin system (RAS). However, both types of hypertension are effectively attenuated by chronic blockade of L-type voltage-dependent calcium channel (L-VDCC). The aim of our study was to evaluate whether the magnitude of BP response elicited by acute nifedipine administration is proportional to the alterations of particular vasoactive systems (SNS, RAS, NO) known to modulate L-VDCC activity. We therefore studied thes e relationships not only in SHR, in which mean arterial pressure was modified in a wide range of 100-210 mm Hg by chronic antihypertensive treatment (captopril or hydralazine) or its withdrawal, but also in rats with augmented RAS activity such as homozygous Ren-2 TGR, pertussis toxin- treated SHR or L-NAME-treated SHR. In all studied groups the magnitude of BP response to nifedipine was proportional to actual BP level and it closely correlated with BP changes induced by acute combined blockade of RAS and SNS. BP response to nifedipine is also closely related to the degree of relative NO deficiency. This was true for both SNS- and RAS-dependent forms of genetic hypertension, suggesting common mechanisms responsible for enhanced L-VDCC opening and/or their upregulation in hypertensive animals. In conclusions, BP response to nifedipine is proportional to the vasoconstrictor activity exerted by both SNS and RAS, indicating a key importance of these two pressor systems for actual L-VDCC opening necessary for BP maintenance., J. Zicha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy