Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renovascular and renal excretory responses to intrarenally infused angiotensin II (Ang II) (1 and 3 ng/min, one dose per rat) were assessed in young (approximately 6 weeks of age) anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats acutely treated with captopril. Urinary excretion of cyclic adenosine monophosphate (cAMP) was also measured in these rats to examine whether Ang II has an enhanced ability to inhibit adenylate cyclase activity in SHR. Ang II (1 ng/min i.r.a.) significantly reduced renal blood flow (RBF) and increased renal vascular resistance (RVR) in SHR but not in WKY rats. At this dose, Ang II produced significant decreases in glomerular filtration rate (GFR), filtration fraction (FF), urine volume (UV) and urinary excretion of sodium (UNaV) and potassium (UkV) in SHR without altering any of these parameters in WKY rats. Ang II at either dose did not cause any increase in systemic blood pressure in either SHR or WKY rats. Ang II (3 ng/min i.r.a.) decreased RBF in both SHR and WKY rats to a similar extent. However, the higher dose of Ang II produced significant decrements in GFR, FF, UV, UNaV and fractional excretion of sodium in SHR but not in WKY rats. Also, Ang II at both the doses significantly decreased urinary cAMP excretion rate in SHR without affecting the same in WKY rats. These data demonstrate that, even during the developmental phase of hypertension, the SHR kidney is more responsive to Ang II as compared with the WKY rat kidney. Also, these results suggest that the ability of Ang II to inhibit renal adenylate cyclase activity in young SHR may be enhanced. The exaggerated renal reactivity to Ang II may be an important determinant of the development of hypertension in SHR.
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PMID:Angiotensin II: enhanced renal responsiveness in young genetically hypertensive rats. 775 79

Injection of N omega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, in dorsolateral periaqueductal gray (PAG) area of freely moving rats at doses from 0.1 to 1 mumol per rat, dose-dependently increased arterial blood pressure (BP). Endothelin-1 (ET-1) injected in the same area at doses from 0.1 to 1 pmol per rat also induced pressor effects. Administration of L-NAME (1 mumol per rat) in the PAG area 10 min before ET-1 significantly (p < 0.01) potentiated ET-1-induced hypertension. Pretreatment with L-arginine (1 mumol per rat), precursor of NO, significantly (p < 0.01) decreased L-NAME-induced potentiation of ET-1 pressor effects. L-Arginine also prevented the ET-induced increase in arterial BP and reversed L-NAME-induced hypertensive effect. Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, reduced either ET-1 or L-NAME pressor effects. Our data suggest the presence of NO synthase in the PAG area, considered an important cerebral area in coordinating physiologic responses such as cardiovascular and respiratory adjustment. Moreover, our results suggest that even at the PAG area level, functional antagonism exists between NO and ET-1, possibly contributing, through sympathetic outflow, to central regulation of arterial BP.
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PMID:Relation between L-arginine-nitric oxide pathway and endothelin-1 effects in periaqueductal gray area of rats. 789 82

In the present study the influence of arcaine (0.01-1 microgram/rat), an in vitro putative non-competitive antagonist of the NMDA receptors, on cardiovascular changes induced by intracerebral administration of N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) has been evaluated. Both NMDA and arcaine were microinjected into the periaqueductal gray (PAG) area of anesthetized rats. Arcaine did not decrease NMDA-induced arterial hypertension and tachycardia, but, in a dose-related manner, increased the NMDA-induced cardiovascular effects. Moreover, treatment with arcaine was not able per se to modify arterial blood pressure and heart rate basal values. Although updated in vitro reports indicate arcaine as a blocker of the NMDA receptors by an open channel mechanism, our in vivo results, at the level of the PAG area, show this not to be true. Indeed the drug may facilitate NMDA receptor activation.
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PMID:Evidence that arcaine increases the N-methyl-D-aspartate-induced cardiovascular effects into the periaqueductal gray area of anesthetized rats. 791 17

We investigated the effect of the polyamine spermidine (SPD) (0.01-1 microgram/rat) on hypertension induced by N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) microinjected into the latero-caudal periaqueductal gray (PAG) area of freely moving rats. Pretreatment with a low dose of SPD (0.01 microgram/rat) significantly increased NMDA-induced hypertension. On the contrary, higher doses of SPD (0.1 and 1 microgram/rat) significantly decreased NMDA-induced cardiovascular changes. SPD alone did not modify arterial blood pressure. Arcaine (1 microgram/rat), a putative antagonist at the polyamine recognition site on NMDA receptors, when microinjected into the PAG area, prevented the negative but not the positive modulatory effects of SPD on the NMDA-induced cardiovascular changes. Pretreatment with SPD did not affect cardiovascular effects induced by quisqualic acid (QUIS), a non-NMDA receptor agonist. These data, in agreement with the in vitro results, suggest that at the level of the PAG area, the polyamines also show multiple actions at NMDA receptors in vivo.
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PMID:Effects of the polyamine spermidine on NMDA-induced arterial hypertension in freely moving rats. 793 16

In this review we have analyzed the present knowledge about the differentiation and growth processes in vascular smooth muscle cells (SMC) in hypertension. The study of smooth muscle (SM) and nonmuscle (NM) myosin isoform expression has permitted us to identify a three-stage specific maturational pathway, namely, fetal, postnatal, and adult. In the renovascular (rabbit) and genetic (rat) models of hypertension, adaptive changes occurring in hypertensive vessels make SMC resemble those found in the early stages of development (smooth muscle plasticity). In fact, based on SM- and NM-myosin isoform distribution, postnatal-type SMC predominate in the arterial media during the early remodeling of the arterial wall that occurs in hypertension, whereas postnatal- and fetal-type SMC predominate in the intimal thickening. Locally produced or activated autocrine/paracrine factors, such as growth factors or cytokines, along with circulating hormones, seem to be involved in the growth response or changes in the differentiation pattern of SMC. Thus, these factors not only play a specific role in the regulation of blood pressure, but also are likely to be responsible for the remodeling of the arterial wall in hypertension.
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PMID:Differentiation and growth of vascular smooth muscle cells in experimental hypertension. 794 70

Very-low-calorie diets lower blood pressure acutely in obese humans and rats. However, refeeding after dietary restriction produces mild hypertension in rats. Refeeding hypertension was characterized in genetically obese spontaneously hypertensive rats (obese SHR, Koletsky rat), a model of genetic obesity and hypertension. Obese SHR were fed a restricted diet (Optifast) for 12 days, refed ad libitum for 28 days, dieted again for 12 days, and then refed 4 days and killed. Control obese SHR and lean SHR littermates were fed ad libitum continuously. Dietary restriction led to rapid weight loss followed by prompt regain to baseline weight after return to unrestricted food intake. Heart rate fell with institution of the low-calorie diet and returned to baseline on refeeding. Blood pressure became elevated during refeeding in dieted obese SHR relative to ad libitum fed obese SHR controls. The fall in blood pressure after ganglionic blockade with chlorisondamine was exaggerated in refed obese SHR, and cardiac beta-adrenergic receptors were downregulated. Both of these findings imply increased sympathetic tone. The left ventricular wall was thicker in the refed obese SHR than in the ad libitum fed obese SHR. Shorter cycles of weight loss and regain in lean SHR led to transient increases in blood pressure and heart rate. Cycles of dietary restriction and refeeding in obese SHR elicit sustained blood pressure elevation via sympathetic activation and exacerbate cardiac hypertrophy. Drastic fluctuations in nutrient intake may not be advantageous in hypertension.
Hypertension 1994 Dec
PMID:Refeeding hypertension in obese spontaneously hypertensive rats. 799 26

Spontaneously hypertensive rats (SHR) are more suitable to heat stroke than are normotensive controls. To determine whether hypertension impairs thermoregulatory reflex cutaneous vasodilation we observed the tail skin vasodilator responses to body heating in male SHR and normotensive Wistar-Kyoto rats (WKY) anesthetized with chloralose and urethan (80 mg/kg and 500 mg/kg ip, respectively). A pulsed-Doppler flow probe was placed on the caudal artery at its origin to monitor tail blood flow (TBF) velocity (the tail skin is the major thermoregulatory organ of the rat), and a catheter was placed in a femoral artery to monitor arterial pressure and heart rate. Internal temperature was measured via a thermistor placed approximately 10 cm down the esophagus into the gastrointestinal tract. During normothermia, TBF was not different between SHR and WKY (0.10 +/- 0.01 vs. 0.15 +/- 0.02 kHz; P > 0.05), whereas tail vascular conductance (TVC) was significantly lower in SHR vs. WKY (0.73 +/- 0.14 vs. 1.88 +/- 0.31 Hz/mmHg; P < 0.05). In response to body heating (tail remained exposed to room temperature), the increases in TBF and TVC were markedly less SHR than in WKY (0.73 +/- 0.14 kHz and 6.03 +/- 1.11 Hz/mmHg vs. 2.61 +/- 0.35 kHz and 22.48 +/- 2.69 Hz/mmHg, respectively). After lumbar sympathectomy, TBF and TVC were not different from the values observed during hyperthermia in both groups. This indicates that the impaired cutaneous vasodilation observed in SHR was not due to failure to withdraw sympathetic vasoconstrictor tone. We conclude that thermoregulatory reflex vasodilation of the cutaneous vasculature is markedly impaired in SHR.
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PMID:Impaired thermoregulatory cutaneous vasodilation in spontaneously hypertensive rats. 800 16

Cholinomimetic agents increase blood pressure and heart rate via central muscarinic cholinoceptors in various species. It was reported that i.c.v. injection of the muscarinic M1 and M3 cholinoceptor selective antagonist, 4-DAMP (4-diphenylacetoxy-N-methyl-piperidine methiodide), inhibited the pressor response to physostigmine, while the M1 selective antagonist, pirenzepine, was ineffective. In the present study, the involvement of muscarinic M2 cholinoceptors in central cholinergic hypertension and tachycardia was investigated. Physostigmine (10-80 micrograms/kg i.v.), a cholinesterase inhibitor, and oxotremorine (20-40 micrograms/kg i.v.), a direct muscarinic cholinoceptor agonist, caused a dose-dependent increase in blood pressure. Additionally, physostigmine induced dose-dependent tachycardiac responses. I.c.v. administration of the muscarinic M2 cholinoceptor antagonists, AF-DX 116 and methoctramine, inhibited both physostigmine (60 micrograms/kg) and oxotremorine (20 micrograms/kg)-induced pressor responses at their lower doses used in this study (100 nmol/rat and 10 nmol/rat, respectively). These findings indicate the partial involvement of postsynaptic muscarinic M2 cholinoceptors. The higher doses of the antagonists (AF-DX 116,300 nmol/rat and methoctramine 30 nmol/rat) potentiated the blood pressure increase due to physostigmine but did not affect that due to oxotremorine. The physostigmine-induced tachycardiac responses were influenced similarly by these antagonists. These results suggest the presence and tonic influence of presynaptic inhibitory muscarinic M2 cholinoceptors.
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PMID:Central muscarinic M2 cholinoceptors involved in cholinergic hypertension. 811 94

N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB), an active-site-directed inhibitor of metalloendopeptidase-24.15, has been shown to lower blood pressure, increase cardiac output and renal blood flow, and potentiate the intravenous bradykinin-induced vasodepressor response. Because in vivo cFP-AAF-pAB can be converted to N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala (a compound with angiotensin converting enzyme inhibitory activity) by metalloendopeptidase-24.11, it is possible that some of its effects are due to angiotensin converting enzyme inhibition. In the present study, we questioned (1) whether cFP-AAF-pAB inhibits angiotensin converting enzyme in vivo and (2) whether cFP-AAF-pAB has renal effects that are independent of its conversion to an angiotensin converting enzyme inhibitor. cFP-AAF-pAB alone (3 mumol in 300 microL per rat) almost abolished the blood pressure response to angiotensin I, suggesting that in vivo it inhibits angiotensin converting enzyme. In rats pretreated with a high dose of enalaprilat (1 mg/kg), cFP-AAF-pAB had no further effect on blood pressure, renal blood flow, or potentiation of the vasodepressor response to bradykinin but still increased glomerular filtration rate by 44 +/- 9% (P < .01); urine volume increased by 118 +/- 10% (P < .001), urinary sodium excretion by 230 +/- 31% (P < .001), urinary potassium excretion by 68 +/- 14% (P < .01), and urinary cyclic GMP by 55 +/- 18% (P < .01). All of these changes were significant compared with enalaprilat/vehicle-treated rats. Fractional excretion of sodium and potassium did not differ from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jan
PMID:Effects of a metalloendopeptidase-24.15. Inhibitor on renal hemodynamics and function in rats. 828 66

CRF is unusual in that it is synthesized and released from the placenta into the circulation in humans, reaching levels in the third trimester that would normally be expected in the hypothalamic portal system during stress. This rise is even more pronounced in pregnancy-induced hypertension and preterm labour. Paradoxically, there is no associated rise of either ACTH or cortisol. This lack of biological response and the stability of the peptide in human (but not rat) plasma in vitro initiated a search for the human CRF-binding plasma protein. This CRF-BP proved to have a molecular mass in the region of 40 kDa, and has been purified to homogeneity. It has an affinity constant in the nanomolar range and when mixed with appropriate amounts of CRF completely inhibits the ACTH-releasing activity of the peptide in vitro. With the cloning of the cDNA for CRF-BP, sufficient pure material has become available for the development of a radioimmunoassay. Although CRF-BP levels in pregnant women are normal in the second trimester, they begin to fall by week 35, reaching approximately 50% of normal values by term. The net effect of this would be an accelerated increase in free, potentially biologically active CRF.
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PMID:Corticotropin-releasing factor and its binding protein in human plasma. 838 5


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