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Biomedical subjects

H Cingolani

Publications and source records attributed to H Cingolani.

5 recordsLinked to original sources

Physiologic and pharmacologic factors that affect myocardial relaxation.

Evaluation of the myocardial relaxation has become important in the last years. An impaired relaxation may precede contractile dysfunctions and even cause heart failure. To treat this impaired lusitropism it is necessary to properly assess the lusitropic state of the heart and understand how drugs affect the cellular mechanisms underlying myocardial relaxation (sarcoplasmic reticulum function, Ca2+ fluxes through the sarcolemma and myofilament Ca2+ sensitivity). Current information regarding these issues is provided in this review. The relative usefulness of the mechanical parameters used to evaluate the lusitropic state of the heart in experimental models applied in pharmacology will also be discussed.

Animals

Relationship between baseline blood pressure and blood pressure decrease after calcium channel blockers in conscious rats.

OBJECTIVE: To determine whether vasodilators produce a fall in mean blood pressure (MBP) that is directly proportional to baseline MBP. DESIGN: The effects on blood pressure of three calcium channel blockers, nitrendipine, nisoldipine and verapamil, were compared with sodium nitroprusside, a drug acting through a different mechanism. The drugs were infused in conscious, unrestrained rats and their effect on MBP was measured. SETTING: Primary experimental. ANIMALS: Animals were divided into three groups according to their baseline MBP: high (greater than 119 mmHg), moderate (91 to 119 mmHg) and normal (less than 91 mmHg). INTERVENTIONS: Five successive infusion rates for each drug were tested in each animal. MBP readings were taken at the end of each infusion period (usually 10 mins). MAIN RESULTS: At the maximal dose infused, nitrendipine (0.57 mg/kg.min) lowered MBP 13 +/- 6 mmHg in the low MBP rats, 51 +/- 4 mmHg in the rats with moderate MBP and 83 +/- 8 mmHg in the rats with high MBP (P < 0.05 within groups). Similar results (ie, the greater the baseline MBP, the greater the fall in MBP) were obtained with nisoldipine and verapamil. In the same groups, sodium nitroprusside (0.096 mg/kg.min) produced a fall of 52 +/- 3 mmHg, 56 +/- 5 mmHg and 54 +/- 13 mmHg, respectively (not significant). CONCLUSIONS: Nitrendipine, nisoldipine and verapamil behave as antihypertensives since their effect increased as a function of the initial MBP, while sodium nitroprusside showed no effect related to baseline MBP.

Animals

The effect of substituted sydnonimines on coronary smooth muscle relaxation and cyclic guanosine monophosphate levels.

In vitro experiments on precontracted canine coronary arteries were performed to study the direct relaxant effects of molsidomine (MOLS) and its active metabolite, SIN-1, and to determine if there is a relationship between effect and cGMP level elevations. The effects of MOLS and SIN-1 were compared with those of a classic vasodilator, nitroglycerin (NTG). At equimolar doses (10(-6)M) SIN-1 exerted greater relaxant effect than NTG (80 +/- 2% and 60 +/- 5%, respectively) in spite of the fact that it produced less of an increase in cyclic guanosine monophosphate (cGMP) levels. cGMP levels fell rapidly after they peaked, but relaxation was maintained. cGMP elevation preceded the induction of relaxation by NTG but not that induced by SIN-1. Relaxation occurred faster after NTG than after SIN-1. Since SIN-1 has a greater relaxant effect than NTG in spite of the fact that SIN-1 induces less of an increase in cGMP levels and the fact that the peak elevation does not precede the onset of relaxation, the causal nexus between GMP level elevation and relaxation effect after sydnonimines should be challenged.

Animals

Effects of angiographic contrast medium on isolated canine coronary arteries.

In isolated canine coronary arteries previously contracted by high potassium concentration, angiographic contrast medium decreased active tension by 61 +/- 2%. The relaxant effect was dose dependent and was not prevented by beta-blockade with d-l-propranolol (10(-5) M). This effect was similar to that obtained with nitroglycerin (10(-6) M), and further relaxation was evident when this vasodilator was administered after exposure to the contrast medium. When arteries were precontracted by alpha-receptor stimulation with norepinephrine (10(-5) M) at normal potassium concentration, a maximal relaxation of 83 +/- 6% was elicited after exposure to contrast medium. The relaxant effect could not be reproduced by a similar increase in osmolarity brought about by addition of sucrose. When arterial strips were processed by radioimmunoassay for dosage of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) after the relaxing action of the contrast medium occurred, a decrease in cAMP from 2.61 +/- 0.86 to 0.63 +/- 0.1 pmol/mg protein (p less than 0.05) was observed, whereas no significant changes in cGMP were detected. These nucleotides do not appear to be involved in the relaxant effect of the dye in the same way as they are when relaxation is elicited by some other coronary vasodilators.

Animals