dihydropyridines and Hypothyroidism

Evaluating the effectiveness of the various options of combination antihypertensive therapy (AHT) in women with arterial hypertension (AH) and metabolic syndrome (MS) and hypothyroidism.. The study included 163 women with hypertension, metabolic syndrome, and hypothyroidism, the median age of 53.5 (48-60) years; in 73 (44.8%) women were diagnosed with subclinical hypothyroidism (SH), 90 (55.2%) - overt hypothyroidism (OH). Patients with both SH and OH, depending on the source of the heart rate (HR) was appointed as one of the following combination of AHT. If heart rate <75 beats/min, patients (n=100) received a combination of the dihydropyridine calcium antagonist (AA) amlodipine 5 mg/day, and angiotensin receptor blockers II (ARB) losartan 50 mg/day, with heart rate >75 beats/min (n=63) - a combination of amlodipine 5 mg/day and imidazoline receptor agonist (IRA) moxonidine 200 micrograms/day. The failure to achieve target blood pressure (BP) after 4 weeks of dose drugs doubled with subsequent evaluation of the effectiveness even after 4 weeks. At baseline and after 6 months of therapy, all patients underwent daily blood pressure monitoring (DBPM).. At 8 weeks, the use of a combination of AA+ARB target BP level was registered in 26 (59%) of 44 women with SH and 34 (60.7%) of the 56 - OH. In the group of women who took the AA+IRA, after 8 weeks of the target blood pressure was observed in 24 (82.8%) of 29 patients with SH and 28 (82.4%) of 34 - to OH. Register the target blood pressure was observed significantly more frequently (p<0,05) when using a combination of AA+IRA compared with AA+ARBs as with SH and OH. As a result of the combination of DBPM AA and ARBs in patients with SH and OG provided a significant reduction in average daily, daytime and nighttime systolic and diastolic blood pressure (SBP and DBP), the time index of SBP and DBP during the day and night hours. The therapy of AA and IRA regardless of the severity of hypothyroidism, there was a significant improvement in all indicators DBPM: average daily, daytime and nighttime SBP and DBP, time index and variability in SBP and DBP during the day and at night. Furthermore, as in the SH and OH significantly more pronounced positive changes most DBPM parameters were recorded using IRA in combination with AA compared with a combination AA+ARB. Significant increase in the number of women with optimal BP daily profile "dipper" observed only when using amlodipine and moxonidine.. In women with hypertension, hypothyroidism and MS, regardless of the severity of decline of thyroid function and combination of the dihydropyridine AA IRA had an advantage over the AA combination with ARBs, since most patients provided achieving target blood pressure and clinically significant positive impact on BPM indicators. The results can be used in selecting the optimal AHT in patients with hypertension, MS, and the manifest subclinical hypothyroidism.

Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dihydropyridines; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Hypothyroidism; Imidazoles; Losartan; Metabolic Syndrome; Middle Aged

Thyroid hormones are known to influence various processes of cell differentiation. Recently, it was reported that hypothyroidism reduces the sensitivity to Ca2+-channel antagonists in the rat uterus. We examined the sensitivity to dihydropyridines of the uterus from mice that had reduced thyroid hormone levels. Isradipine relaxed with the same potency precontracted uterine muscle strips from control and hypothyroid mice, independently from a pseudo-pregnant state. These results demonstrate that hypothyroidism does not change dihydropyridine sensitivity (i.e., the pattern of Ca2+-channel expression) in the murine uterus.

Topics: Animals; Calcium Channel Blockers; Calcium Channels, L-Type; Cell Differentiation; Dihydropyridines; Female; Hypothyroidism; In Vitro Techniques; Isradipine; Mice; Mice, Inbred C57BL; Muscle, Smooth; Thyroid Hormones; Uterine Contraction; Uterus

1. Alterations in the cardiac alpha 1-adrenoceptor and its subtypes in hypothyroid rats were studied by radioligand binding assays and reverse transcription-polymerase chain reaction (RT-PCR). Hypothyroidism was created by feeding rats with 0.2% 2-thiouracil solution instead of daily drinking water for 20 days. 2. The density of cardiac alpha 1-adrenoceptors (Bmax) was increased from 67.5 +/- 4.3 fmol/mg in control rats to 81.1 +/- 7.2 fmol/mg (P < 0.05) in hypothyroid rats. 3. Compared with control rats, in hypothyroid rats the percentages of high-affinity sites for (+)-niguldipine and 5-methylurapidil were increased from 13.8 +/- 5.6 and 31.9 +/- 6.3%, respectively, to 24.9 +/- 7.3 and 45.5 +/- 2.4%, respectively (both P < 0.05), while those for BMY7378 were decreased from 37.2 +/- 8.9 to 23.8 +/- 8.4% (P < 0.05), respectively. The percentage of high-affinity sites for WB4101 was not significantly different in control and hypothyroid rats (43.3 +/- 9.1 and 39.4 +/- 3.6%, respectively). 4. Reverse transcription-PCR experiments revealed that the steady state levels of mRNA for alpha 1A- and alpha 1B-adrenoceptors were increased, while those for alpha 1D-adrenoceptor were decreased in the hearts of hypothyroid rats. 5. The concentration-contraction response curves for noradrenaline in the presence of a beta-adrenoceptor antagonist in control and hypothyroid rats showed that the maximal response was reduced from 344 +/- 58 to 200 +/- 23 mg, respectively (P < 0.05). 6. The data suggest that in hypothyroid rats the total number of cardiac alpha 1-adrenoceptors is increased. The change is subtype-selective, with levels of alpha 1A- and alpha 1B-adrenoceptors being increased and levels of alpha 1D-adrenoceptors being reduced. Furthermore, the positive inotropic response mediated by alpha 1-adrenoceptors is reduced in hypothyroid rats.

Topics: Adrenergic alpha-Antagonists; Animals; Atrial Function; Binding, Competitive; Dihydropyridines; Dioxanes; DNA Primers; Heart Atria; Hypothyroidism; Male; Myocardial Contraction; Norepinephrine; Phenethylamines; Piperazines; Polymerase Chain Reaction; Protein Binding; Radioligand Assay; Rats; Receptors, Adrenergic, alpha; RNA, Messenger; Tetralones; Thiouracil