Sympathetic hyperactivity and relative NO deficiency are characteristic alterations in both genetic and salt hypertension. The contribution of these abnormalities to blood pressure (BP) maintenance can be determined in conscious rats using a consecutive blockade of particular vasoactive systems. Thus, the contribution of pressor effects of angiotensin II to the maintenance of high BP is usually small, but the role of renin-angiotensin system in the development of hypertension mediated by central and peripheral effects of angiotensin II on sympathetic activity is highly important. This is even true in angiotensin-dependent hypertension of heterozygous Ren-2 transgenic rats in which sympathetic hyperactivity is increasing with age. Central sympathoexcitation in this hypertensive model can be inhibited by lower losartan doses than peripheral angiotensin II-dependent vasoconstriction. This experimental model also yielded important knowledge on nephroprotective effects of new therapeutic drugs - endothelin receptor type A blockers. A considerable part of sympathetic vasoconstriction is dependent on the interaction of Ca2+ sensitization (RhoA/Rho kinase pathway) and Ca2+ influx (through L-VDCC). The blockade of these pathways prevents a major part of sympathetic vasoconstriction. Ca2+ sensitization seems to be attenuated in genetic hypertension in order to compensate increased Ca2+ influx. In contrast, enhanced Ca2+ sensitization is a hallmark of salt sensitivity in Dahl rats in which salt hypertension is dependent on increased Ca2+ influx. The attention should also be paid to the impairment of arterial baroreflex sensitivity which permits enhanced BP responses to pressor or depressor stimuli. Some abnormalities can be studied in blood vessels isolated from hypertensive rats but neither conduit arteries nor mesenteric resistance arteries represent the vascular beds decisive for the increased peripheral resistance and high BP. Keywords: Sympathetic vasoconstriction, NO-dependent vasodilatation, Calcium sensitization, Calcium influx, Arterial baroreflex, Spontaneously hypertensive rats, Salt hypertensive Dahl rats, Ren-2 transgenic rats, RAS blockade, SNS blockade, NOS inhibition, Endothelin, Vascular contraction and relaxation, Isolated conduit and resistance arteries, EDCF, PGI2, BKCa channels.

• MeSH
• Hypertension * physiopathology   metabolism   MeSH
• Blood Pressure physiology   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Renin-Angiotensin System physiology   MeSH
• Sympathetic Nervous System * physiopathology   metabolism   MeSH
• Vasodilation * physiology   drug effects   MeSH
• Vasoconstriction * physiology   drug effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Hypertension is the most prevalent cardiovascular disease of the adult population and is closely associated with serious cardiovascular events. The burden of hypertension with respect to vascular and other organ damage is greater in women. These sex differences are not fully understood. The unique feature in women is their transition to menopause accompanied by profound hormonal changes that affect the vasculature that are also associated with changes of blood pressure. Results from studies of hormone replacement therapy and its effects on the cardiovascular system are controversial, and the timing of treatment after menopause seems to be important. Therefore, revealing potential sex- and sex hormone-dependent pathophysiological mechanisms of hypertension in experimental studies could provide valuable information for better treatment of hypertension and vascular impairment, especially in postmenopausal women. The experimental rat models subjected to ovariectomy mimicking menopause could be useful tools for studying the mechanisms of blood pressure regulation after menopause and during subsequent therapy.

• MeSH
• Hormone Replacement Therapy MeSH
• Hypertension * MeSH
• Cardiovascular Diseases * epidemiology   MeSH
• Blood Pressure physiology   MeSH
• Rats MeSH
• Menopause physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The agonists of alpha(2)-adrenergic receptors such as clonidine, rilmenidine or monoxidine are known to lower blood pressure (BP) through a reduction of brain sympathetic outflow but their chronic antihypertensive effects in rats with low-renin or high-renin forms of experimental hypertension were not studied yet. Moreover, there is no comparison of mechanisms underlying BP reduction elicited by chronic peroral (po) or intracerebroventricular (icv) clonidine treatment. Male salt-sensitive Dahl rats fed 4% NaCl diet and Ren-2 transgenic rats were treated with clonidine administered either in the drinking fluid (0.5 mg/kg/day po) or as the infusion into lateral brain ventricle (0.1 mg/kg/day icv) for 4 weeks. Basal BP and the contributions of renin-angiotensin system (captopril 10 mg/kg iv) or sympathetic nervous system (pentolinium 5 mg/kg iv) to BP maintenance were determined in conscious cannulated rats at the end of the study. Both peroral and intracerebroventricular clonidine treatment lowered BP to the same extent in either rat model. However, in both models chronic clonidine treatment reduced sympathetic BP component only in rats treated intracerebroventricularly but not in perorally treated animals. In contrast, peroral clonidine treatment reduced angiotensin II-dependent vasoconstriction in Ren-2 transgenic rats, whereas it lowered residual blood pressure in Dahl rats. In conclusions, our results indicate different mechanisms of antihypertensive action of clonidine when administered centrally or systemically.

• MeSH
• Angiotensin II pharmacology   MeSH
• Antihypertensive Agents pharmacology   MeSH
• Sodium Chloride MeSH
• Clonidine pharmacology   MeSH
• Hypertension * chemically induced   drug therapy   MeSH
• Hypotension * MeSH
• Blood Pressure MeSH
• Rats MeSH
• Sodium Chloride, Dietary MeSH
• Rats, Inbred Dahl MeSH
• Rats, Transgenic MeSH
• Renin MeSH
• Sympathetic Nervous System MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Angiotensin II MeSH
• Antihypertensive Agents MeSH
• Sodium Chloride MeSH
• Clonidine MeSH
• Sodium Chloride, Dietary MeSH
• Renin MeSH

Calcium sensitization mediated by RhoA/Rho kinase pathway can be evaluated either in the absence (basal calcium sensitization) or in the presence of endogenous vasoconstrictor systems (activated calcium sensitization). Our aim was to compare basal and activated calcium sensitization in three forms of experimental hypertension with increased sympathetic tone and enhanced calcium entry-spontaneously hypertensive rats (SHR), heterozygous Ren-2 transgenic rats (TGR), and salt hypertensive Dahl rats. Activated calcium sensitization was determined as blood pressure reduction induced by acute administration of Rho kinase inhibitor fasudil in conscious rats with intact sympathetic nervous system (SNS) and renin-angiotensin system (RAS). Basal calcium sensitization was studied as fasudil-dependent difference in blood pressure response to calcium channel opener BAY K8644 in rats subjected to RAS and SNS blockade. Calcium sensitization was also estimated from reduced development of isolated artery contraction by Rho kinase inhibitor Y-27632. Activated calcium sensitization was enhanced in all three hypertensive models (due to the hyperactivity of vasoconstrictor systems). In contrast, basal calcium sensitization was reduced in SHR and TGR relative to their controls, whereas it was augmented in salt-sensitive Dahl rats relative to their salt-resistant controls. Similar differences in calcium sensitization were seen in femoral arteries of SHR and Dahl rats.

• MeSH
• Animals, Genetically Modified MeSH
• Hypertension etiology   genetics   metabolism   pathology   MeSH
• rho-Associated Kinases antagonists & inhibitors   genetics   MeSH
• Rats MeSH
• Humans MeSH
• Rats, Inbred Dahl MeSH
• Rats, Inbred SHR MeSH
• Signal Transduction drug effects   MeSH
• Sympathetic Nervous System metabolism   pathology   MeSH
• Calcium administration & dosage   metabolism   MeSH
• Vasoconstriction genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• rho-Associated Kinases MeSH
• Calcium MeSH