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Biomedical subjects

I Kobrin

Publications and source records attributed to I Kobrin.

83 records · Page 5Linked to original sources
PubMed1981

Cyclic AMP generation in medulla oblongata and hypothalamus of hypertension-prone and -resistant rats.

Accumulation of cAMP induced by noradrenaline (NA) was higher in the medulla oblongata (MO) of hypertension-prone (H) than in resistant (N) rats, 113 +/- 3 vs. 72 +/- 4 (p less than 0.01). In the hypothalamus (HYP) it was higher in N than in H rats, 148 +/- 8 vs. 92 +/- 6 (p less than 0.01). In both anterior and posterior HYP, the accumulation of cAMP was significantly higher in N than in H rats. cAMP accumulation, in the presence of increasing concentrations of phosphodiesterase inhibitor, showed significant strain differences in both MO and HYP. The observed strain differences in cAMP may be pertinent to the disparate susceptibility to hypertension of H and N rats.

Animals↗
PubMed1981

Distinguishing traits in the Sabra hypertension-prone (SBH) and hypertension-resistant (SBN) rats.

Distinct differences in central and peripheral noradrenaline (NA) were observed in the hypertension prone (SBH) and resistant (SBN) strain, derived from the Hebrew University SABRA rats. In the medulla oblongata NA concentration was 90% higher and tyrosine hydroxylase activity 88% lower in SBN when compared to SBH, suggesting marked strain differences in NA turnover. In this area, NA-induced cAMP generation was higher in SBH than in SBN, while the hypothalamus, the reverse situation was present. The relevance of hypertension of the reciprocal cAMP changes is still uncertain. The concentration of NA in heart tissue was significantly higher in SBN than in SBH. Doca-salt treatment caused hypertension and depletion of atrial NA in SBH, but had no effect on either blood pressure or atrial NA in SBN rats. The results suggest that resistance to hypertension in SBN rats is associated with decreased NA turnover in medulla oblongata and reduced activity of cardiac neuronal sympathetic endings.

Animals↗
PubMed1980

Cyclic AMP generation in hypothalamus of hypertension-prone and -resistant rats.

1. This noradrenaline-induced accumulation of cyclic AMP is decreased in both the anterior and the posterior hypothalamus of hypertension-prone as compared with resistant rats, but is similar in the cortex. 2. The noradrenaline-induced accumulation of cyclic AMP is decreased in the posterior hypothalamus as compared with the anterior hypothalamus of both strains. 3. The decreased sensitivity to phosphodiesterase inhibitor in the hypothalamus of hypertension-prone as compared with resistant rats suggests that strain differences in phosphodiesterase activity may exist. 4. Since differences in cyclic AMP were found in the hypothalamus and the medulla oblongata, regions involved in blood pressure control, but not in the cortex, they may be relevant to the diverse susceptibility to hypertension of hypertension-prone and resistant rats.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1980

The Sabra hypertension prone (H) and hypertension resistant (N) rat strain.

By selective inbreeding of the Hebrew University Sabra rat, we have obtained a hypertension prone (H) and a hypertension resistant (N) substrain. The criteria for selection was the blood pressure response to DOCA-salt. The outstanding element of our model is the N rat with its remarkable resistance to hypertension. When compared to H, the N rat presents the following characteristics: 1. The blood pressure of experimentally naive N rats is significantly lower at comparable ages, in both sexes. 2. N rats are resistant to both DOCA-salt and renal clip hypertension. 3. In the medulla oblongata (MO) of N rats, the noradrenaline (NA) content is significantly higher and the activity of tyrosine hydroxylase is significantly lower. 4. In the MO of N rats, the sensitivity of the NA dependent cAMP generating system is significantly decreased. 5. In the atrium of N rats, the NA content is significantly higher, and is unaffected by DOCA-salt treatment. The results suggest that genetic differences in catecholamine metabolism may account for the disparate susceptibility to hypertension of the two strains.

Animals↗
PubMedDate not supplied

Evaluating the safety of mibefradil, a selective T-type calcium antagonist, in patients with chronic congestive heart failure.

Mibefradil is a novel calcium antagonist belonging to a new chemical class of benzimidazolyl-substituted tetraline derivatives. The safety of mibefradil in patients with mild-to-moderate chronic congestive heart failure (CHF) due to coronary heart disease was assessed in a randomized, double-masked, placebo-controlled, multiple-ascending-dose trial in 45 patients. Patients were assigned to receive one of five dose levels (6.25, 12.5, 25, 50, or 100 mg/d) of mibefradil or placebo according to a randomization list. If safety variables remained stable, the subsequent group of patients was randomized to the next higher dose. The safety variables assessed included New York Heart Association class, vital signs, and ejection fraction. Patients were evaluated at baseline and day 8 of the dosing period. Mibefradil did not worsen clinical or cardiac variables. Approximately 23.3% (7 of 30) of the mibefradil-treated patients reported one or more adverse events compared with 13.3% (2 of 15) of the placebo group. The incidence of adverse events was not dose dependent. In summary, short-term oral dosing of mibefradil did not worsen measures of cardiac function in 30 patients with mild-to-moderate CHF.

Administration, Oral↗
PubMedDate not supplied

Effectiveness of combined nifedipine and propranolol treatment in hypertension.

The long-term antihypertensive effect of combined nifedipine and propranolol therapy was assessed in an open trial in 26 hypertensive patients (19 men, seven women, mean age 53 years). On propranolol alone (160 to 240 mg/day), the patients' average sitting blood pressure was 192 +/- 5/114 +/- 2 mm Hg. Propranolol was continued in a fixed dose and nifedipine was added in a dose that was gradually increased from 30 to 90 mg/day to achieve blood pressure (BP) values below 160/95 mm Hg. Twenty-two patients remained on the combined regimen for 14 to 30 weeks. Their BP decreased to 136 +/- 3/84 +/- 2 mm Hg on an average daily dose of 59.5 mg nifedipine. Seventeen of the 22 subjects were subsequently treated sequentially with propranolol alone, combined therapy, and nifedipine alone, to assess the relative efficacy of each mode of therapy. The combined regimen was found to be more effective than either drug alone. Side effects occurred in 13 of 26 patients. Four dropped out 4 to 11 weeks after starting nifedipine because of either intolerable flushing (2), allergic rash (1), or headache (1). Nine subjects experienced mild reactions that were well tolerated. It is concluded that the combined use of propranolol and nifedipine is effective in the long-term treatment of moderately severe hypertension and offers an alternative therapeutic approach that deserves further evaluation.

Adult↗