In the current work we present some pharmacological characteristics of ten new analogues of bradykinin (Arg–Pro–Pro–Gly–Phe–Ser–Pro–Phe–Arg) modified in the N-terminal part of the molecule with a variety of acyl substituents. Of the many acylating agents used previously with B2 receptor antagonists, the following residues were chosen: 1-adamantaneacetic acid (Aaa), 1-adamantanecarboxylic acid (Aca), 4-tert-butylbenzoic acid (t-Bba), 4-aminobenzoic acid (Aba), 12-aminododecanoic acid (Adc), succinic acid (Sua), 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 3-(4-hydroxyphenyl)propionic acid and 6-hydroxy-2-naphthoic acid. Biological activity of the compounds was assessed in the in vivo rat blood pressure test and the in vitro rat uterus test. Surprisingly, N-terminal substitution of the bradykinin peptide chain itself with aforementioned groups resulted in antagonists of bradykinin in the pressor test and suppressed agonistic potency in the uterotonic test. These interesting findings need further studies as they can be helpful for designing more potent B2 receptor blockers.

Subject of this study is the predictive value of baseline heart rate (HR) response to simulated diving. Twentyseven male volunteers aged 20-25 performed apneic face immersion in cold water, while ECG was recorded. Both the initial HR increase and the following bradycardic response significantly correlated to resting HR. To optimally estimate the reference HR (mean HR or the longest 512-RR-intervallong time series or minimum of moving HR average at given lengths), we compared three different approaches, based on the best correlations between the evoked responses, HRV measures and resting baseline. Our data indicate lack of universal HR reference useful to predict resulting diving response. The longest RRi observed across preceding time window is apparently the best indicator of the diving bradycardic response, while the initial HR increase and time of voluntary apnea corresponds to the longtime HR average. Index Terms-diving reflex, baseline heart rate, HRV

A characteristic feature of the cardiac response to diving is the uncertainty in predicting individual course. The aim of the study was to determine whether resting regulatory heart rate determinants assessed before diving may be predictors of cardiac response in a simulated diving test. The research was conducted with 65 healthy volunteers (37 women and 28 men) with an average age of 21.13 years (20–27 years) and a BMI of 21.49 kg/m2 (16.60–28.98). The simulated diving test consisted of stopping breathing after maximum inhaling and voluntarily immersing the face in water (8–10 °C) for as long as possible. The measurements included heart rate variability (HRV) analysis before diving and determination of the course of the cardiac response to diving—minimum and maximum heart rate (HR). The results indicate that minimum HR during diving (MIN_div) is dependent on the short-term HRV measures, which proves the strong influence of the parasympathetic system on the MIN_div. The lack of dependence of MIN_div on short-term HRV in women may be associated with differences in neurogenic HR regulation in women and men. In conclusion, cardiac response to simulated diving is strictly dependent on the autonomic regulation of the heart rhythm under resting conditions. The course of the cardiac response to diving and its relationship with resting HRV appears to be gender dependent.

In the present work, achiral non-coded amino acids, N-(Bzl)-Gly, X(1) or X(2) , were substituted at position 7 of the model B(2) receptor antagonist [D-Arg(0) , Hyp(3) , Thi(5, 8) , D-Phe(7) ]-BK. The N-terminal amino group of the analogues was either free or acylated with 1-Aca or Aaa. Biological activity of the compounds was assessed in the in vitro rat uterus test and the in vivo rat blood pressure test. The X(1) (7) substitution resulted in a decrease in antagonistic potency of the new peptide in both assays. The X(2) (7) and N-(Bzl)-Gly(7) substituted analogues showed weak agonistic properties in the rat uterus test. Interestingly, the latter compound exhibited dual activity in the pressor test, i.e. intrinsic vasodepressor action and at the same time a weak antagonistic effect. Acylation of the N-terminus enhanced antagonistic properties of the resulting peptides in the rat blood pressure test in the case of compounds containing X(1) or X(2) modification. Our studies provide new information about structure-activity relationship of the BK antagonists which may be helpful for designing more potent B(2) receptor blockers.

The regular cardiac response to immersion of the face in cold water is reduction in heart rate (HR). The highly individualized and unpredictable course of the cardiodepressive response prompted us to investigate the relationship between the cardiac response to face immersion and the resting HR. The research was conducted with 65 healthy volunteers (37 women and 28 men) with an average age of 21.13 years (20–27 years) and a BMI of 21.49 kg/m2 (16.60–28.98). The face-immersion test consisted of stopping breathing after maximum inhaling and voluntarily immersing the face in cold water (8–10 °C) for as long as possible. Measurements included determination of minimum, average, and maximum HR at rest and minimum and maximum HR during the cold-water face-immersion test. The results indicate a strong relationship between the cardiodepressive reaction of the immersion of the face and the minimum HR before the test, as well as a relationship between the maximum HR during the test and the maximum HR at rest. The results also indicate a strong influence of neurogenic HR regulation on the described relationships. The parameters of the basal HR can, therefore, be used as prognostic indicators of the course of the cardiac response of the immersion test.