M Kohzuki, M Yasujima, P F Liu, K Obara, M Kanazawa, K Yoshida, T Saito, T Sato, K Abe
{"title":"Cardiovascular and renal protective effects of losartan in spontaneously hypertensive rats with diabetes mellitus.","authors":"M Kohzuki, M Yasujima, P F Liu, K Obara, M Kanazawa, K Yoshida, T Saito, T Sato, K Abe","doi":"10.1111/j.1440-1681.1995.tb02956.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02956.x","url":null,"abstract":"<p><p>1. Cardiovascular and renal benefits of a specific angiotensin II (AII) receptor antagonist, losartan (LOS), were assessed in diabetic rats with renal impairment. 2. Uninephrectomized SHR made diabetic by streptozotocin administration were given LOS (5 mg/kg per day, i.p.) alone, captopril (CAP) (50 mg/kg per day, i.p.) alone, or a combination of CAP and LOS via osmotic minipumps for 8 weeks. 3. Both CAP alone and LOS alone completely blocked the development of hypertension in diabetic SHR in the same manner. CAP + LOS did not enhance the antihypertensive effects of LOS alone or CAP alone. 4. CAP + LOS, LOS alone and CAP alone significantly decreased urinary protein excretion and serum creatinine to the same extent. 5. These results indicate that both LOS and CAP exert antihypertensive and renoprotective effects in this model: these actions are mainly through inhibition of AII production.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S366-7"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02956.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Nakagawa, I Tanaka, S Suga, Y Ogawa, N Tamura, M Goto, A Sugawara, T Yoshimasa, H Itoh, M Mukoyama
{"title":"Preparation of a monoclonal antibody against mouse brain natriuretic peptide (BNP) and tissue distribution of BNP in mice.","authors":"M Nakagawa, I Tanaka, S Suga, Y Ogawa, N Tamura, M Goto, A Sugawara, T Yoshimasa, H Itoh, M Mukoyama","doi":"10.1111/j.1440-1681.1995.tb02874.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02874.x","url":null,"abstract":"<p><p>1. In order to explore the significance of brain natriuretic peptide (BNP), a cardiac hormone secreted from the ventricle, in mice, we prepared a monoclonal antibody against mouse BNP (mBNP) and established a specific radioimmunoassay (RIA) for mBNP. 2. A monoclonal antibody, KY-mBNP-I, was prepared by the fusion of mouse myeloma cells X63-Ag8.653 with spleen cells of the BALB/c mouse immunized with synthetic mBNP[108-121] conjugated to bovine thyroglobulin. KY-mBNP-I belonged to an IgG2a subclass and showed a high affinity for mBNP (Ka = 1.8 x 10(11) mol/L-1). 3. The RIA established that using KY-mBNP-I was highly sensitive and specific for mBNP, with an IC50 value of 3 fmol/tube and cross-reactivities of less than 0.003% with related natriuretic peptides. mBNP-like immunoreactivity (mBNP-LI) was detected in the mouse atrium (0.35 +/- 0.02 nmol/g), ventricle (20.5 +/- 0.5 pmol/g) and kidney (0.50 +/- 0.05 pmol/g), but not in other tissues including brain. 4. Gel filtration analysis revealed that the major component of tissue mBNP-LI was co-eluted with synthetic mBNP[77-121], a 45-amino acid mature peptide. 5. The monoclonal antibody and RIA for mBNP established here will provide useful tools to investigate the functional significance of BNP in mice, coupled with the genetic engineering approach.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S186-7"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02874.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of felodipine treatment and withdrawal on blood pressure and cardiovascular structure in New Zealand genetically hypertensive rats.","authors":"J M Ledingham, E L Phelan, M A Cross, R Laverty","doi":"10.1111/j.1440-1681.1995.tb02939.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02939.x","url":null,"abstract":"<p><p>1. Four groups of New Zealand genetically hypertensive (GH) rats were treated with felodipine as follows: (A) from ages 4-12 weeks; (B) 4-20 weeks; (C) 4-12 weeks then withdrawn from felodipine till age 20 weeks; and (D) 12-20 weeks. 2. Effects on blood pressure (BP), left ventricular (LV) weight and the structure of myograph-mounted mesenteric resistance arteries (MRA) were measured. 3. BP was about 170 mmHg in 4 week old GH rats and did not change substantially from this value in groups A and B but rose to over 230 mmHg in untreated controls. In rats of group D, started on felodipine at 12 weeks, BP fell rapidly and was 173 mmHg at 20 weeks. On withdrawal of felodipine at 12 weeks (group C) BP rose rapidly and exceeded control levels at 20 weeks. 4. LV mass was significantly lower (P < 0.001) in all groups (A, B and D) killed while on felodipine but rose to control levels in the rats taken off felodipine. 5. In the four treated groups there were no significant changes in MRA structure (lumen diameter, medial thickness, media/lumen ratio and volume of medial tissue) as measured on the myograph. 6. Felodipine induces substantial falls in BP in GH rats which are sufficient to prevent cardiac hypertrophy but do not alter MRA structure. Resistance artery structure in GH rats does not seem to relate to the level of hypertension, and may therefore not have a necessary role in the pathogenesis of this hypertensive strain.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S326-8"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02939.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y Habuchi, L L Lu, S Okamoto, T Komori, H Takahashi, J Morikawa, M Yoshimura
{"title":"Decreased sensitivity to beta-adrenergic stimulation of the ventricular cells isolated from the spontaneously hypertensive rat heart.","authors":"Y Habuchi, L L Lu, S Okamoto, T Komori, H Takahashi, J Morikawa, M Yoshimura","doi":"10.1111/j.1440-1681.1995.tb02840.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02840.x","url":null,"abstract":"<p><p>1. The stimulatory effects of isoproterenol on the L-type Ca2+ current (ICa) were compared between the control (WKY) and hypertensive (SHR) rat heart cells, using the patch-clamp method. 2. The current density and the shape of the current-voltage relationship for ICa were not different between the two groups. However, the maximal percentage increase in response to isoproterenol was smaller in SHR (+91% in SHR and +81% in WKY), and the ED50 was significantly higher in SHR (0.081 mu mol/L in SHR and 0.020 mu mol/L in WKY). IBMX, a potent phosphodiesterase inhibitor, significantly increased the isoproterenol-stimulated ICa in SHR, but not in WKY. These results suggest an impaired cAMP production in SHR heart cells.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S105-6"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02840.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K Tsuda, S Tsuda, I Nishio, Y Masuyama, M Goldstein
{"title":"Synergistic effects of Bay K 8644 and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats.","authors":"K Tsuda, S Tsuda, I Nishio, Y Masuyama, M Goldstein","doi":"10.1111/j.1440-1681.1995.tb02968.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02968.x","url":null,"abstract":"<p><p>1. In the present study, we examined the effects of Bay K 8644, a dihydropyridine (DHP)-sensitive Ca2+ channel agonist, and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats (SHR). 2. In the preliminary studies using Sprague-Dawley rats, Bay K 8644 by itself had no significant effects on the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release in a dose-related fashion. The facilitatory effects of bradykinin on norepinephrine release were potentiated by Bay K 8644. 3. In SHR, Bay K 8644 significantly increased the stimulation-evoked norepinephrine release from hypothalamic slices. However, exposure of slices to Bay K 8644 caused no significant effects on norepinephrine release in Wistar-Kyoto (WKY) rats. The effects of Bay K 8644 in combination with bradykinin on the stimulation-evoked norepinephrine release were also greater in SHR than in WKY rats. 4. These results demonstrate that Bay K 8644 significantly potentiated the facilitatory effects of bradykinin on norepinephrine release in rat hypothalamus. The finding indicates a possible interaction of bradykinin with DHP-sensitive Ca2+ channels in the central nervous system. Furthermore, the pronounced effects of Bay K 8644 and bradykinin in SHR suggest that bradykinin-related Ca2+ channels might have a role in the regulation of norepinephrine release in the hypothalamus of SHR.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S54-7"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02968.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alteration of baroreceptor and chemoreceptor reflexes in spontaneously hypertensive rats.","authors":"H Ohta, W T Talman","doi":"10.1111/j.1440-1681.1995.tb02970.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02970.x","url":null,"abstract":"<p><p>1. Electrical stimulation of the aortic depressor nerve elicited depressor and bradycardiac responses in both spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats, but in spontaneously breathing animals responses were weaker in SHR than in WKY. 2. Responses did not significantly differ in artificially ventilated animals except that high stimulation intensity elicited significantly greater bradycardiac responses in WKY. A decrease in ventilatory rate occurred in both strains. 3. Electrical stimulation of the carotid sinus nerve (CSN) elicited an initial pressor response followed by a depressor response with a minimal change in heart rate in either strain. The pressor response in SHR was greater than in WKY. Depressor responses in SHR were weaker than those in WKY with or without artificial ventilation. CSN stimulation increased ventilatory rate in both strains but the frequency-related responses differed at higher stimulation intensity. 4. These results suggest that there are alterations in the function of central or afferent components of chemoreceptor and baroreceptor reflexes in SHR in addition to previously described structural changes at the level of peripheral sensory receptors.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S60-1"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02970.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Studies on pregnancy hypertension and IUGR-SFD: effects of drugs on the blood vessels in the placenta of pregnant SHRSP.","authors":"I Fuchi, K Noda, Y Matsubara","doi":"10.1111/j.1440-1681.1995.tb02920.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02920.x","url":null,"abstract":"<p><p>1. Based upon our previous work, we came to the conclusion that a decrease in placental blood volume was a possible factor behind intrauterine growth retardation (IUGR) in pregnancy-induced hypertension. 2. In a second study, we used an image analysis system to measure cross-sectional areas and wall thicknesses of central blood vessels of the spiral artery, the so-called 'central artery'. 3. It was thought that one of the more basic factors behind IUGR in pregnancy-induced hypertension might possibly be narrowings and spasms of the maternal placental blood vessels. 4. In this study, we found that the three drugs we used (MgSO4 center dot 7H2O, Solcoseryl and KCl) all resulted in an enlargement of the cross-sectional areas of the maternal blood vessels, and that MgSO4 center dot 7H2O, in particular, also relaxed maternal blood vessel spasms in SHRSP placenta.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S286-7"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02920.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhanced contractile responses mediated by different 5-HT receptor subtypes in basilar arteries, superior mesenteric arteries and thoracic aortas from stroke-prone spontaneously hypertensive rats.","authors":"Y Nishimura, A Suzuki","doi":"10.1111/j.1440-1681.1995.tb02986.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02986.x","url":null,"abstract":"<p><p>1. The contractile effects of 5-hydroxytryptamine (5-HT) in isolated ring preparations of basilar arteries (BA) thoracic aortas (TA) and superior mesenteric arteries (SMA) from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were investigated pharmacologically. 2. The pD2 values (expressed as a negative logarithm of of EC50) for 5-HT in BA of SHRSP were greater than those of WKY. Increased pD2 values for 5-HT were also found in SMA and TA of SHRSP when compared to WKY. 3. Ketanserin (a 5-HT2 antagonist) produced a biphasic displacement of the concentration-response curves for 5-HT in BA of WKY and SHRSP but elicited a parallel rightward shift of the 5-HT curve in SMA and TA of the two groups. 4. 5-CT (a 5-HT1 agonist)-induced contractions and their pD2 values in the presence of ketanserin were larger in BA of SHRSP than in those of WKY, while 5-CT did not contract SMA or TA in either group. 5. No significant difference was found in the contractile response induced by alpha-methyl-5-HT (a 5-HT2 agonist) in BA from SHRSP and WKY, while the pD2 values for alpha-methyl-5-HT were increased in SMA and TA from SHRSP when compared to WKY. 6. These results suggest that the hyperresponsiveness to 5-HT found in SHRSP arteries may be mediated by different 5-HT receptor subtypes, that is, by 5-HT1 in BA and by 5-HT2 in SMA and TA.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S99-101"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02986.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20027880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of vascular contraction by ionic matrix surfaces of the smooth muscle cell: changes in SHR?","authors":"G M Kravtsov, C Y Kwan","doi":"10.1111/j.1440-1681.1995.tb02898.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02898.x","url":null,"abstract":"<p><p>1. KCl-induced contractions in aortic rings of spontaneously hypertensive rats (SHR) and two normotensive strains, Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats, were studied. 2. The contraction elicited by isotonic Na-free, KCl solution containing 2.5 mmol/L Ca and 1 mmol/L Mg was concentration-dependently inhibited by Na and K. Maximal inhibition was induced by 20 mmol/L NaCl in WKY and SHR (65 and 85%, respectively) and by 60 mmol/L NaCl in SD (50%). KCl (10-40 mmol/L) had no effect on SD but produced almost full relaxation in WKY and about 50% relaxation in SHR. 3. Isotonic Ca-free, Na-free high Mg (2 mmol/L), K-solution caused strong phasic contractions in WKY and SHR, but weak responses in SD. 4. Aortic rings of SD, WKY and SHR developed strong, sustained and reproducible contractions in isotonic Ca-free, Na-free, K-solution containing EDTA, which were fully relaxed by 1.2, 1.6 and 8 mmol/L Na, respectively. 5. We suggest that the primary mechanism of KCl-contraction is potential-independent competition between monovalent and divalent cations for binding sites on both surfaces of the plasma membrane (e.g. K with Mg and Na with Ca) and that differences in aortic contractility in SHR, WKY and SD merely reflect strain differences in the composition of the ionic matrix, independent of hypertension.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S237-9"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02898.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20028031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S S Huang, S A Khosrof, R J Koletsky, B A Benetz, P Ernsberger
{"title":"Characterization of retinal vascular abnormalities in lean and obese spontaneously hypertensive rats.","authors":"S S Huang, S A Khosrof, R J Koletsky, B A Benetz, P Ernsberger","doi":"10.1111/j.1440-1681.1995.tb02850.x","DOIUrl":"https://doi.org/10.1111/j.1440-1681.1995.tb02850.x","url":null,"abstract":"<p><p>1. The obese SHR (Koletsky rat; SHR-k) is a unique animal model for the study of microvascular changes associated with genetic obesity, spontaneous hypertension, endogenous hyperlipidaemia, and hyperinsulinaemic, non-insulin dependent diabetes mellitus (Type II). 2. Lean and obese SHR-k exhibit retinal vascular changes which have not been previously characterized and are more severe than previously described in other animal models of experimental hypertension or non-insulin dependent diabetes. 3. Progressive retinal capillary dropout, capillary cell changes, vascular tortuosity and dilatation are severe. Vessels form elevated varicose vascular tortuosities which leak fluorescein dye and which are more frequent in the obese SHR-k. This study suggests that lean and obese SHR may be unique models for the study of multivariate factors in the pathogenesis of ischaemic neovascular proliferation.</p>","PeriodicalId":75710,"journal":{"name":"Clinical and experimental pharmacology & physiology. Supplement","volume":"22 1","pages":"S129-31"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.1995.tb02850.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20026279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}